FLU VACCINES

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FLUZONE
Influence Virus Vaccine
Protection for all ages
6 months and beyound

Click on a topic below to learn more about Fluzone vaccine

Characteristics
Fluzone vaccine contains three inactivated (killed) influenza viruses ... [MORE]

Indication and Usage
Fluzone vaccine is indicated for active immunization against influenza ... [MORE]

Safety Considerations
Fluzone vaccine is not appropriate for everyone ... [MORE]

Vaccination Recommendations
Dosing is recommended by age and Fluzone vaccine presentation ... [MORE]

Storage and Handling
Fluzone vaccine should NOT be frozen ... [MORE]

Presentations
Fluzone vaccine is available in multiple presentations ... [MORE]

Indication
Fluzone vaccine is given for active immunization in persons 6 months of age and older against influenza disease caused by influenza virus subtypes A and type B contained in the vaccine.

Safety Information

Side effects to Fluzone vaccine are soreness, pain, and swelling at the injection site; fever, fatigue, and muscular pain. Other side effects may occur. Fluzone vaccine should not be administered to anyone with a history of serious allergic reaction to any vaccine component, including eggs, egg products, or thimerosal (the only Fluzone vaccine product containing thimerosal is the multi-dose vial), or to persons who have been previously diagnosed with Guillain-Barré syndrome (GBS). If you notice any other problems or symptoms following vaccination, please contact your health-care professional immediately. Vaccination with Fluzone vaccine may not protect all individuals.

For more information about Fluzone vaccine, talk to your health-care professional.

Last modified: 11/16/09

LINK FOR MORE: www.fluzone.com/?fa=protect/fluzone/about

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Fluvirin®
2009-2010 FORMULA

DOSE IS AGE RELATED:

TIV* Fluzone Sanofi Pasteur 0.25mL prefilled syringe 0 6–35 mos 1 or 2† Intramuscular§
0.5 mL prefilled syringe 0 36 mos and older 1 or 2† Intramuscular§
0.5 mL vial 0 36 mos and older 1 or 2† Intramuscular§
5.0 mL multidose vial 25 6 mos and older 1 or 2† Intramuscular§

Novartis Vaccines and Diagnostics Limited BLA 1750
April 2009 Page 1 of 20
Influenza Virus Vaccine

HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use FLUVIRIN® (Influenza Virus Vaccine) safely and effectively. See full prescribing information for FLUVIRIN®.
FLUVIRIN® (Influenza Virus Vaccine)
Suspension for Intramuscular Injection
2009-2010 Formula
Initial US Approval: 1988
INDICATIONS AND USAGE
•
FLUVIRIN® is an inactivated influenza virus vaccine indicated for active immunization of persons 4 years of age and older against influenza disease caused by influenza virus subtypes A and type B contained in the vaccine (1).
•
FLUVIRIN® is not indicated for children less than 4 years of age because there is evidence of diminished immune response in this age group (8.4).
DOSAGE AND ADMINISTRATION
Children
•
4 to 8 years of age: 0.5-mL dose via intramuscular injection, one or two doses.
Children aged 4 to 8 years should receive 2 doses of vaccine separated by at least 4 weeks, if they have not been vaccinated previously at any time with any influenza virus vaccine. Children aged 4 to 8 years who received only 1 dose in their first year of vaccination in the previous season should receive 2 doses of vaccine separated by at least 4 weeks. Children aged 4 to 8 years who have been vaccinated with two doses of any influenza virus vaccine in the previous season, or with one dose in the year prior to the previous season, should receive only one dose. (2.2)
•
9 years and older: A single 0.5-mL intramuscular injection (2.2).
Adults
•
A single 0.5-mL intramuscular injection (2.2).
DOSAGE FORMS AND STRENGTHS
FLUVIRIN®, a sterile suspension for intramuscular injection, is supplied in two presentations:
•
Prefilled syringe, 0.5-mL. Thimerosal, a mercury derivative used during manufacture, is removed by subsequent purification steps to a trace amount (≤ 1 mcg mercury per 0.5-mL dose). (3, 11)
•
Multidose vial, 5-mL. Contains thimerosal, a mercury derivative (25 mcg mercury per 0.5-mL dose). Thimerosal is added as a preservative. (3,11)

Each 0.5-mL dose contains 15 micrograms (mcg) of influenza virus hemagglutinin (HA) from each of the following 3 viruses: A/Brisbane/59/2007, IVR-148 (H1N1); A/Uruguay/716/2007, NYMC X-175C (H3N2) (an A/Brisbane/10/2007-like virus); and B/Brisbane/60/2008. (3, 11)
Vial and Syringe leaflet text
Novartis Vaccines and Diagnostics Limited BLA 1750
April 2009 Page 2 of 20
CONTRAINDICATIONS
•
History of systemic hypersensitivity reactions to egg proteins, or any other component of FLUVIRIN®, or life-threatening reactions to previous influenza vaccinations. (4.1, 11)
WARNINGS AND PRECAUTIONS
•
If Guillain-Barré syndrome has occurred within 6 weeks of receipt of prior influenza vaccine, the decision to give FLUVIRIN® should be based on careful consideration of the potential benefits and risks. (5.1)
•
Immunocompromised persons may have a reduced immune response to FLUVIRIN®. (5.2)
ADVERSE REACTIONS
The most frequently reported adverse reactions are mild hypersensitivity reactions (such as rash), local reactions at the injection site, and influenza-like symptoms. (6)
To report SUSPECTED ADVERSE REACTIONS contact Novartis Vaccines at 1-800-244-7668, or VAERS at 1-800-822-7967 and www.vaers.hhs.gov.
DRUG INTERACTIONS
•
Do not mix with any other vaccine in the same syringe or vial. (7.1)
•
Immunosuppressive therapies may reduce immune response to FLUVIRIN®. (7.2)
USE IN SPECIFIC POPULATIONS
•
Safety and effectiveness of FLUVIRIN® have not been established in pregnant women, nursing mothers or children less than 4 years of age. (8.1, 8.3, 8.4)•
Antibody responses were lower in the geriatric population than in younger subjects. (8.5)
See 17 for PATIENT COUNSELING INFORMATION.
Revised: April 2009

LINK: www.novartisvaccines.com/us/downloads/Fluvirin_PI_2009_2010.pdf

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AGRIFLU

18 yrs and older

AGRIFLU - Novartis Vaccines and Diagnostics, Inc. 1.14.1.3 Draft US Package Insert
26 October 2010 Confidential Page 1 of 11

11. DESCRIPTION
AGRIFLU, Influenza Virus Vaccine, for intramuscular injection is a trivalent inactivated influenza virus vaccine prepared from virus propagated in the allantoic cavity of embryonated hens¡¯ eggs inoculated with an influenza virus suspension containing kanamycin and neomycin sulphate. Each of the influenza virus strains is harvested and clarified separately by centrifugation and filtration prior to inactivation with formaldehyde. The inactivated virus is concentrated and purified by zonal centrifugation. The surface antigens, hemagglutinin and neuraminidase, are obtained from the influenza virus particle by further centrifugation in the presence of cetyltrimethylammonium bromide (CTAB), a process which removes most of the internal proteins. The CTAB is removed from the vaccine preparation by subsequent purification steps.

AGRIFLU is a sterile clear aqueous suspension and is formulated to contain a total of 45 mcg hemagglutinin (HA) per 0.5-mL dose in the recommended ratio of 15 mcg HA of each of the following three influenza virus strains recommended for the 2010/2011 influenza season: A/California/7/2009, NYMC X-181 (H1N1); A/Victoria/210/2009, NYMC X-187 (H3N2) (an A/Perth/16/2009-like virus); and B/Brisbane/60/2008.
AGRIFLU is manufactured and formulated without thimerosal or any other preservative.
Each 0.5 mL dose may contain residual amounts of egg proteins (<0.4 mcg), formaldehyde (¡Ü10 mcg), polysorbate 80 (¡Ü50 mcg), and CTAB (¡Ü12 mcg). Each dose may also contain residual amounts of neomycin (¡Ü0.02 mcg by calculation) and kanamycin (¡Ü0.03 mcg by calculation), which are used during the initial stages of manufacture. The tip caps of the syringes may contain natural rubber latex. The syringe plunger does not contain natural rubber latex.

CONTINUED: www.fda.gov/downloads/BiologicsBloodVaccines/Vaccines/ApprovedProducts/UCM192127.pdf

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FLUARIX

GlaxoSmithKline Biologicals

INDICATIONS AND USAGE
FLUARIX® is indicated for active immunization for the prevention of disease caused by influenza virus subtypes A and type B contained in the vaccine. FLUARIX is approved for use in persons 3 years of age and older.

Limitations of Vaccine Effectiveness

Vaccination with FLUARIX may not protect all susceptible individuals.

FLUARIX is formulated without preservatives. FLUARIX does not contain thimerosal. Each 0.5-mL dose also contains octoxynol-10 (TRITON® X-100) ≤0.085 mg, α-tocopheryl hydrogen succinate ≤0.1 mg, and polysorbate 80 (Tween 80) ≤0.415 mg. Each dose may also contain residual amounts of hydrocortisone ≤0.0016 mcg, gentamicin sulfate ≤0.15 mcg, ovalbumin ≤0.05 mcg, formaldehyde ≤5 mcg, and sodium deoxycholate ≤50 mcg from the manufacturing process.

The tip caps of the prefilled syringes may contain natural rubber latex. The rubber plungers do not contain latex.

CONTINUED: us.gsk.com/products/assets/us_fluarix.pdf

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TIV FluLaval ID Biomedical Corp. of Quebec, a subsidiary of GlaxoSmithKine 5.0 mL multidose vial 25 18 yrs and older 1 Intramuscular§[/b]

Safety information for FLULAVAL was collected in 2 randomized, controlled clinical trials, one in the United States (IDB707-105) and the second in Canada (SPD707-104). The safety population from these trials includes 1,049 adults 18 years of age and older vaccinated with products representative of the licensed formulation of FLULAVAL. The US study included subjects 18 to 64 years of age who were randomized to receive FLULAVAL (N = 721) or a US-licensed trivalent, inactivated influenza virus vaccine (FLUZONE) (N = 279). The Canadian study compared 4 vaccine groups: FLULAVAL, a similar investigational formulation of FLULAVAL with reduced thimerosal, and 2 Canadian-licensed trivalent influenza vaccines.

CONTINUED: www.rxlist.com/flulaval-drug.htm

TIV Afluria¶ CSL Biotherapies 0.5 mL prefilled syringe 0 9 yrs and older 1 Intramuscular§
TIV High Dose** Fluzone High-Dose Sanofi Pasteur 0.5 mL prefilled syringe 0 65 yrs and older 1 Intramuscular§

Thimerosal, a mercury derivative, is not used in the manufacturing process for the single dose presentations; therefore these products contain no preservative. The multi-dose presentation contains thimerosal, added as a preservative; each 0.5 mL dose contains 24.5 mcg of mercury.

CONTINUED: www.rxlist.com/afluria-drug.htm
LAIV†† FluMist§§ MedImmune 0.2 mL sprayer, divided dose 0 2–49 yrs 1 or 2† Intranasal

What are the ingredients in FluMist?

Active Ingredient: FluMist contains 3 influenza virus strains that are weakened (A(H1N1), A(H3N2), and B).
Inactive Ingredients: monosodium glutamate, gelatin, arginine, sucrose, dibasic potassium phosphate, monobasic potassium phosphate, and gentamicin

FluMist does not contain preservatives.

WARNINGS AND PRECAUTIONS------------------------

Do not administer FluMist to children <24 months of age because of increased risk of hospitalization and wheezing observed in clinical trials. (5.1)

FluMist should not be administered to any individuals with asthma or children < 5 years of age with recurrent wheezing because of the potential for increased risk of wheezing post vaccination. (5.2)

If Guillain-Barré syndrome has occurred with any prior influenza vaccination, the decision to give FluMist should be based on careful consideration of the potential benefits and risks. (5.3)

Administration of FluMist, a live virus vaccine, to immunocompromised persons should be based on careful consideration of the potential benefits and risks. (5.4)

Safety has not been established in individuals with underlying medical conditions predisposing them to wild-type influenza infection complications. (5.5)

CONTINUED: www.fda.gov/downloads/BiologicsBloodVaccines/Vaccines/ApprovedProducts/UCM123743.pdf

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TABLE. Influenza vaccines recommended by the Advisory Committee on Immunization Practices (ACIP) for different age groups — United States, 2010–11 season

LINK: www.cdc.gov/flu/protect/vaccine/vaccines.htm

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OCTOBER 29, 2009

Caution on Additive Slows Vaccine

The wait for H1N1 vaccinations stretched to five hours Tuesday at the county health department in Provo, Utah. Four thousand doses had arrived overnight.

The U.S. is trying to hasten delivery of an H1N1 vaccine but is avoiding one shortcut to getting more shots available quickly: the use of a special booster ingredient called an adjuvant.

Countries in Europe and elsewhere are using adjuvants to stretch limited H1N1-vaccine supplies. Some countries have used adjuvant in flu shots for years.

But the U.S. has been wary of adding an extra ingredient to its flu-shot formula -- which has decades of safety data behind it -- particularly as people voice concerns about the safety of swine-flu shots.

The U.S. this spring ordered about $700 million of adjuvant for possible use during an H1N1 pandemic, but it has taken few steps toward using it.

U.S. officials said they haven't ruled out using adjuvants in the future but don't believe they are necessary now. The H1N1 vaccine doesn't require a booster to provide adequate protection, they said

There are no adjuvants licensed for use with flu vaccines in the U.S. They haven't been used as widely, so their safety record isn't as extensive as that of adjuvant-free vaccines, officials said

"When you give products to millions of healthy people, you want to have as much data as you can available," said Jesse Goodman, chief scientist at the Food and Drug Administration.
Some flu experts in Europe find the U.S. position puzzling, especially with vaccine supplies running behind schedule. When it comes to adjuvant, the U.S. is "very, very conservative. And far beyond what I think is reasonable," said David Fedson, a vaccine expert in France who has worked in industry and served on the U.S. Advisory Committee on Immunization Practices. "In a mild pandemic maybe it doesn't make a difference. In a major pandemic, maybe it could make a difference."

The debate comes as the pace of U.S. deliveries of swine-flu vaccine is picking up. About 10 million new doses are expected from manufacturers this week, said Nicole Lurie, assistant secretary for preparedness and response for the U.S. Department of Health and Human Services. Those new doses would bring officials closer to the 28 million to 30 million they estimated would be shipped to warehouses by the end of the month.

[The adjuvants used outside of the U.S. are emulsions of oil and water designed to boost the effectiveness of the main ingredient in flu vaccine, which is called antigen. Adjuvants allow for less antigen to be used per shot, which is useful in a pandemic because antigen-production facilities are limited. Shots that contain adjuvant in Europe use half or less of the antigen used in U.S. shots.

One adjuvant, made by Novartis AG, has been used in Europe for 12 years in seasonal flu shots for elderly people. Novartis said more than 40 million doses have been given with a good safety record. That gave Europe's main medical regulator more confidence in approving the use of adjuvant in swine-flu vaccine, experts said. Adjuvants from Novartis and GlaxoSmithKline PLC are being used in H1N1 shots in Europe.

"I think the Europeans said, 'We will not have enough vaccine if we go for the un-adjuvanted vaccine.' And they wanted to make sure that the European population had access to adequate vaccine," said Martin Friede, an adjuvant expert with the World Health Organization in Geneva. Europeans also wanted to use adjuvants to help "free up antigen for use in the rest of the world," he said.

Vaccine makers have held extensive talks with the FDA about approval, but no companies have applied yet -- in part because the FDA has set a high bar for proving that the additives are both beneficial and safe, companies said.

Compared with European regulators, "the hurdle was higher" at the FDA for using adjuvants in flu shots, said Andrin Oswald, the head of Novartis's vaccines business.

Dr. Goodman of the FDA said the agency has been talking with makers of adjuvants and a clinical trial with adjuvanted H1N1 vaccine is under way. A trial with vaccine for H5N1, the still-circulating virus that causes avian flu, is planned for early 2010. The government has been making "major investments in trying to move the science of adjuvants along and to study adjuvanted vaccine," he said.

Because no adjuvants are yet licensed for use, the FDA would have to issue an emergency authorization for their use. Such an authorization would take four to six weeks, said Dr. Lurie of Health and Human Services -- by which point officials expect the vaccine to be much more widely available. It would also likely be a tough sell to skeptics who are casting doubt on the safety of adjuvant-free vaccines.

"I can't imagine what we would be up against," Dr. Lurie said.
Dr. Friede of the WHO said the adjuvants have been widely tested in adults and have shown a solid safety record. They have also been studied in children, he said, though less extensively.

www.medscape.org/viewarticle/727478

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Test Your Adjuvant IQ: Ten Things You Need to Know About Adjuvanted Influenza Vaccines CME/CE
William Schaffner, MD

Authors and Disclosures

Posted: 08/27/2010

Adjuvanted Influenza Vaccines: Truth or Consequences

The events of the 2010-2011 influenza season highlighted some of the challenges of pandemic preparedness and raised questions about how to best respond to those challenges in the future. A good bit of academic discussion and Internet chatter have focused on the use of adjuvanted influenza vaccines in the United States. Against the backdrop of vaccine anxiety and strong antivaccine sentiment in the United States, some experts are saying that the use of adjuvants is a critical component of preparedness and will be necessary should a virus such as the H5N1 become pandemic. In addition, the question has been raised, Why not adjuvanted vaccines for seasonal influenza? The purpose of this Q&A is to dispel some of myths and inaccuracies circulating about vaccine adjuvants in the context of influenza vaccines.

What Is an Adjuvanted Vaccine and How Is It Different From a Nonadjuvanted Vaccine?
An adjuvanted vaccine is a vaccine to which a substance called an adjuvant (discussed below) has been added. The goal of vaccination is to generate a strong enough immune response to the antigen in the vaccine to provide long-term protection against the targeted pathogen (ie, virus). Adjuvants are added to some vaccines to generate a more effective immune response. The ideal adjuvant is sufficiently potent, but does not excessively activate the innate immune system to the point of toxicity.


What Is a Vaccine Adjuvant?

A vaccine adjuvant is a pharmacologic agent that is added to a vaccine to increase the antigenic response to the vaccine. Hundreds of natural and synthetic compounds have been identified as potential vaccine adjuvants, but only a few have been determined to be safe. As of this writing, the aluminum salt alum is the only adjuvant approved for use in any vaccine in the United States. The US Food and Drug Administration (FDA) has approved vaccines with alum adjuvants for the prevention of many diseases. A list of vaccine ingredients sorted by vaccine, prepared by the US Centers for Disease Control and Prevention (CDC), can be found at www.cdc.gov/vaccines/pubs/pinkbook/downloads/appendices/B/excipient-table-2.pdf. Only emulsion (squalene oil-in-water-based), virosomal (reconstituted influenza virus envelopes devoid of inner core and genetic information), and combination (aluminum salt plus MPL [monophosphoryl lipid A]) adjuvants are approved for use in seasonal influenzavaccines in Europe.Are

Adjuvanted Vaccines New?

Adjuvants are not new. Alum was introduced as an adjuvant in the United States in the 1930s, and MF59-adjuvanted and virosomal-adjuvanted seasonal influenza vaccines have been used in Europe for more than a decade. The MF59-adjuvanted seasonal influenza vaccine is approved for use in adults, and the virosomal-adjuvanted vaccine is approved for use in children and adults in Europe. It is estimated that more than 40 million doses of adjuvanted seasonal influenza vaccine have been administered in Europe.

Is an Adjuvanted Seasonal Influenza Vaccine Licensed for Use in the United States?

As of this writing, no adjuvanted seasonal influenza vaccine is approved for use in the United States. The FDA approves adjuvants only when they are used in combination with vaccines. The seasonal influenza vaccines licensed for use in the United States are the trivalent inactivated vaccine (intramuscular injection), approved for all persons 6 months of age and older, and the live attenuated trivalent vaccine (nasal spray), approved for healthy, nonpregnant persons 2-49 years of age. Neither of these vaccines contains an adjuvant.

Were Adjuvanted Influenza Vaccines Used in the 2009-2010 H1N1 Pandemic?[/b

]Yes, adjuvanted influenza pandemic vaccines were used in many countries, including Canada, during the 2009-2010 H1N1 pandemic. However, adjuvanted influenza pandemic vaccines were not used in the United States.

If There Is Another Pandemic, Will Adjuvanted Influenza Vaccines Be Used in the United States?

There is the potential for use of adjuvanted influenza vaccines in the United States during a pandemic. The United States has a stockpile of more than 300 million doses of proprietary adjuvants for Emergency Authorization Use if necessary. An example of necessary use would be an H5N1 pandemic; humans cannot mount a good immune response to the H5N1 vaccine unless it is adjuvanted.

What Are the Potential Benefits of Adjuvanted Seasonal Influenza Vaccines?

The potential benefits of adjuvanted seasonal influenza vaccines are heightened immunogenicity and broadened immunity (cross-protection against drifted strains), which potentially translates to better protection from influenza, fewer influenza-related complications, and lower morbidity and mortality. Adjuvants can also be used to reduce the amount of antigen per vaccine dose or the number of immunizations required. This is called antigen sparing. Antigen sparing is desirable because more vaccine can be manufactured to protect more people in a briefer time. The trivalent MF59-adjuvanted seasonal influenza vaccine has mostly been evaluated in elderly persons in Europe. Those studies compared the vaccine against nonadjuvanted conventional seasonal influenza vaccines using hemagglutinin inhibition assays to measure immunogenicity. A meta-analysis of 20 clinical trials involving the use of MF59-adjuvanted vaccine in more than 10,000 elderly persons confirmed greater immunogenicity in the elderly.

Why Do We Need a New Vaccine Formulation Nearly Every Year?

We need a new vaccine formulation nearly every year because of the phenomena known as antigenic drift and antigenic shift. See Improving Vaccine Effectiveness: Luxury or Necessity? in this collection for an explanation of antigenic drift and shift. Each year, the World Health Organization and the CDC collect data from 94 nations on the influenza viruses that circulated the previous year to make an educated guess as to which viruses are likely to circulate in the coming fall. On the basis of their findings, the FDA issues orders to manufacturers in February for a vaccine that includes the 3 virus strains that are most likely to be circulating the following winter.

What Are the Most Common Side Effects of the Adjuvanted Seasonal Influenza Vaccines in Use in Europe?

The most common side effect is pain at the injection site. A meta-analysis of safety data from over 2000 elderly persons who received 1 or more MF59-adjuvanted vaccinations showed that the most common side effect was pain at the injection site, which was more frequent in patients who received the adjuvanted vaccine than in those who received the nonadjuvanted vaccine. In addition, no immediate, allergic-type reactions occurred after immunization. Erythema and induration occurred in more than 10% of vaccine recipients, but most local reactions were rated as mild and of short duration. A single-center study also showed that injection site pain and muscle aches were the most common reactions and were more common in patients who received the MF59-adjuvanted vaccine.

Is Squalene Dangerous?

Squalene is not dangerous. Nearly a decade ago, squalene oil was reported to be the experimental anthrax vaccine ingredient that caused the Persian Gulf War syndrome in many veterans; antibodies to squalene were detected in the blood of most patients with this syndrome. This caused widespread concern about the safety of influenza vaccines containing squalene oil-based adjuvants, such as MF59. Subsequently, it was shown that squalene is poorly immunogenic; low titers of antibodies to squalene can be detected in sera from healthy individuals; and neither the presence of antisqualene antibodies nor their titer is significantly increased by immunization with vaccines containing squalene oil-based adjuvant.

Supported by an independent educational grant from Novartis Vaccines

[josie]

As of this writing, no adjuvanted seasonal influenza vaccine is approved for use in the United States

If the adjuvanted seasonal influenza vaccine is used effectively in Europe, why is it not used here in the US also?

The potential benefits of adjuvanted seasonal influenza vaccines are heightened immunogenicity and broadened immunity (cross-protection against drifted strains), which potentially translates to better protection from influenza, fewer influenza-related complications, and lower morbidity and mortality. Adjuvants can also be used to reduce the amount of antigen per vaccine dose or the number of immunizations required. This is called antigen sparing. Antigen sparing is desirable because more vaccine can be manufactured to protect more people in a briefer time. The trivalent MF59-adjuvanted seasonal influenza vaccine has mostly been evaluated in elderly persons in Europe. Those studies compared the vaccine against nonadjuvanted conventional seasonal influenza vaccines using hemagglutinin inhibition assays to measure immunogenicity. A meta-analysis of 20 clinical trials involving the use of MF59-adjuvanted vaccine in more than 10,000 elderly persons confirmed greater immunogenicity in the elderly.

This only heightens my curiosity as to why we don't use it...

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Dec 31, 2010 18:33:24 GMT -5 josie said:

As of this writing, no adjuvanted seasonal influenza vaccine is approved for use in the United States

If the adjuvanted seasonal influenza vaccine is used effectively in Europe, why is it not used here in the US also?

The potential benefits of adjuvanted seasonal influenza vaccines are heightened immunogenicity and broadened immunity (cross-protection against drifted strains), which potentially translates to better protection from influenza, fewer influenza-related complications, and lower morbidity and mortality. Adjuvants can also be used to reduce the amount of antigen per vaccine dose or the number of immunizations required. This is called antigen sparing. Antigen sparing is desirable because more vaccine can be manufactured to protect more people in a briefer time. The trivalent MF59-adjuvanted seasonal influenza vaccine has mostly been evaluated in elderly persons in Europe. Those studies compared the vaccine against nonadjuvanted conventional seasonal influenza vaccines using hemagglutinin inhibition assays to measure immunogenicity. A meta-analysis of 20 clinical trials involving the use of MF59-adjuvanted vaccine in more than 10,000 elderly persons confirmed greater immunogenicity in the elderly.

This only heightens my curiosity as to why we don't use it...

Good evening Josie, AND HAPPY NEW YEAR!

I agree that the above sounds reasonable without further research into health concern issues.

The adjuvants in vaccines in question have not been adequately tested to meet FDA standards/approval. HOWEVER, consider the following article: Swine Flu Scare: It’s All about The Adjuvant!
Herb Newborg

August 5, 2009

The U. S. government has paid pharmaceutical companies $7.9 billion* since 2004 to develop the capacity to mass vaccine the entire U.S. population by 2011. Under the perceived threat of H1N1, these plans have been accelerated to include the use of a non FDA approved chemical adjuvant suspected of causing Gulf War Syndrome, circumventing the FDA approval process for this potentially life threatening chemical.

In 2005, the Department of Health and Human Services (HHS) published a plan with two specific goals that relate to vaccines. The first goal was to have in place by 2011 domestic production capacity sufficient to supply vaccine to the entire U.S. population within six months of the onset of a pandemic. The second goal was to stockpile enough doses of vaccine to inoculate 20 million people as soon as possible after the onset of a pandemic.

As of September 15, 2008, HHS had yet to determine how best to build and develop the capacity to create the hundreds of millions of doses necessary for such an ambitious undertaking. Three options were identified which could possibly achieve the stated goal by 2011:

Continue to fund and expand funding for the egg-based vaccine antigen production currently utilized in the production of seasonal flu vaccine (viruses are grown in hens’ eggs). Toward this end, HHS has budgeted $600 million to offer capital subsidies to manufacturers to build egg-based production facilities in addition to $176 million already awarded.

Continue to fund and expand funding for cell-based vaccine antigen production (for example, viruses grown in the kidneys of dogs) widely used to manufacture vaccine against polio, chicken pox, measles, mumps, and rubella. To date, HHS has obligated $1.3 billion to promote the development of new cell-based influenza vaccines.

Fund next generation vaccine manufacturing, based on the use of recombinant-DNA technology. Recombinant vaccines are made by splicing antigen producing genes into the DNA of another organism (pigs, monkeys, birds, insects, etc.) The modified organisms then reproduce to provide bulk quantities of antigen. Recombinant techniques are already in use to make vaccines against hepatitis B and human papillomavirus.

Link to companies working on Recombinant-DNA-Technolody.
www.jazdlifesciences.com/pharmatech/leaf/Contract-Manufacturing/Recombinant-DNA-Technology.htm
All three scenarios had major drawbacks.

Using egg-based vaccine antigen to provide the quantities necessary to vaccinate all 300 million Americans with 2 doses each would require massive infrastructure build up. Despite the $176 million already awarded to manufactures, additional funds would be needed and FDA approvals (not expected until 2011) are necessary in order to even begin to approach the desired number of vaccine doses. It is estimated that the two companies awarded egg-based funding combined could produce only 125 million doses, even after the infrastructure upgrades, and not until 2011.

Using cell-based antigen to provide the quantities necessary to vaccinate all 300 million Americans with 2 doses each would also require massive infrastructure build up. A plant could produce 25 million pandemic-influenza doses at 90 micrograms per dose. It would take about nineteen plants with that capacity to produce 475 million doses. If the cost of construction, bringing the plant online, and obtaining the FDA’s approval averaged $400 million per plant, the total cost of the expanded capacity would be $7.6 billion. If each plant cost $600 million, the total would be $11.4 billion. This capacity would not be available until 2011-2012.

Next generation or recombinant-DNA is not an attractive option, as most recombinant influenza vaccines have not yet advanced past early-stage clinical trials. These vaccines could be 10 years or more away from the market. HHS has yet to fund their development for use against influenza, in part because it has chosen to build on the decades of experience in using cell culture to produce other vaccines. However, HHS plans to award contracts worth $155 million for the development of next-generation vaccines in the near future.

So where does the capacity to mass vaccinate the entire population stand after our $7.9 billion investment?
We currently have a stockpile of 22.5 million doses of the H5N1 antigen for the feared Avian flu pandemic that never materialized. The cost to maintain this stockpile for just two circulating strains of H5N1 is about $2.2 billion annually. Influenza vaccine typically expires after two years; 15 million doses have expired or will expire soon.

In addition, we have stockpiled 268 million doses of what appears to be the wildcard in the whole equation. This is what is known as an adjuvant. An adjuvant is a chemical that can be added to vaccines to reduce the amount of active ingredient (antigen) needed per dose of vaccine by “turbo-charging” the immune system response in the recipient. This could potentially stretch the supply, providing six times as many doses from the same quantity of antigen.

This would solve many, if not all of the issues regarding capacity to mass vaccinate the entire population. Instead of investing in building additional plants and hiring workers to produce antigen, the funds could be used to purchase proprietary, patented chemical adjuvants.

The only problem is: these chemicals are not FDA approved. They have not been FDA safety tested. We have no idea if they are safe and in fact have every reason to suspect that they are not.

Despite this fact, the U.S. has already purchased at least 312 million doses of two proprietary, patented adjuvants: MF59 from Novartis and ASO3 from GSK. These purchases took place despite the fact that neither chemical has been FDA approved for use in a vaccine. The manufacturers have not yet even obtained FDA approval for Phase I clinical trials in the U.S., the first step toward approval of any new drug, vaccine or adjuvant.On average, it takes a little over a decade for a drug to move from preclinical development to the marketplace. Before a vaccine enters human testing, the developer conducts laboratory (in vitro) and laboratory animal (in vivo) testing to determine whether the product will be safe enough for researchers to proceed to clinical trials.

The developer must obtain the FDA’s approval to begin clinical trials through the submission of an investigational new drug, or IND, application. Clinical trials typically have three phases. Phase I focuses on the vaccine’s safety and generally involves fewer than 100 human subjects. The purpose of Phase II, which typically involves several hundred subjects, is to expand Phase I safety data and identify whether and at what dose the vaccine elicits a protective immune response. Phase III typically involves thousands of people and is used to document effectiveness and develop additional safety data (notably concerning the incidence and severity of side effects) required for licensing. Clinical trials generally last five to seven years. If all three phases of the clinical development are successful, the developer may submit a biologics license application, or BLA, to the FDA for review. If the FDA approves the application, the developer launches the new vaccine, a process that includes training its sales force and increasing production capabilities to meet the anticipated demand.

It appears that the U.S. is prepared to skip all of the normally required safety and efficacy procedures and allow for the massive testing of this novel adjuvant on at least 25% of the 12,000 Americans serving as paid clinical trial participants in tests of the new H1N1 vaccine, despite documented U.S. government warnings that adjuvanted vaccines can induce more pronounced side effects than ordinary vaccines, a definite downside because vaccines, unlike most other pharmaceuticals, are given to healthy people.
To date, the Food and Drug Administration has never approved an adjuvanted vaccine for influenza. Other adjuvanted vaccines currently licensed for use in the United States—against diphtheria, tetanus, hepatitis A, and hepatitis B—are made with aluminum. But aluminum adjuvants do not reduce the amount of antigen needed by enough to substantially increase the amount of vaccine that would be available during a pandemic.

The FDA has not approved a human vaccine containing a new type of adjuvant in many years, as all other types of adjuvants have thus far produced too many side effects to meet the FDA’s standards.

The reason introducing this chemical without the required safety and efficacy testing is so objectionable is that both of these proprietary adjuvants contain squalene.

Oil-based vaccination adjuvants like squalene have been proved to generate concentrated, unremitting immune responses over long periods of time according to a 2000 article in The American Journal of Pathology.

A 2000 study published in the American Journal of Pathology demonstrated a single injection of the adjuvant squalene into rats triggered “chronic, immune-mediated joint-specific inflammation,” also known as rheumatoid arthritis. The researchers concluded the study raised questions about the role of adjuvants in chronic inflammatory diseases.

What happens when Squalene is injected into humans?

Your immune system recognizes squalene as an oil molecule native to your body. It is found throughout your nervous system and brain. In fact, you can consume squalene in olive oil and not only will your immune system recognize it, you will also reap the benefits of its antioxidant properties.

The difference between “good” and “bad” squalene is the route by which it enters your body. Injection is an abnormal route of entry which incites your immune system to attack all the squalene in your body, not just the vaccine adjuvant.

Your immune system will attempt to destroy the molecule wherever it finds it, including in places where it occurs naturally, and where it is vital to the health of your nervous system, according to award-winning investigative journalist Gary Matsumoto, who explains there is a “close match between the squalene-induced diseases in animals and those observed in humans injected with this oil: rheumatoid arthritis, multiple sclerosis and systemic lupus erythematosus.”
“There are now data in more than two dozen peer-reviewed scientific papers, from ten different laboratories in the US, Europe, Asia and Australia, documenting that squalene-based adjuvants can induce autoimmune diseases in animals…observed in mice, rats, guinea pigs and rabbits. Sweden’s Karolinska Institute has demonstrated that squalene alone can induce the animal version of rheumatoid arthritis. The Polish Academy of Sciences has shown that in animals, squalene alone can produce catastrophic injury to the nervous system and the brain. The University of Florida Medical School has shown that in animals, squalene alone can induce production of antibodies specifically associated with systemic lupus erythematosus,” writes Matsumoto.

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We got our first hint at the dangers of these proprietary adjuvants when they were secretly tested on soldiers during the Gulf War.

Gulf War veterans with Gulf War Syndrome (GWS) received anthrax vaccines which contained squalene. MF59 (the Novartis squalene adjuvant) was an unapproved ingredient in experimental anthrax vaccines and has since been linked to the devastating autoimmune diseases suffered by countless Gulf War vets according to data published in the February 2000 and August 2002 issues of Experimental and Molecular Pathology.

The Department of Defense made every attempt to deny that squalene was indeed an added contaminant in the anthrax vaccine administered to Persian Gulf war military personnel – deployed and non-deployed – as well as participants in the more recent Anthrax Vaccine Immunization Program (AVIP).

However, the FDA discovered the presence of squalene in certain lots of AVIP product. A test was developed to detect anti-squalene antibodies in GWS patients, and a clear link was established between the contaminated product and all the GWS sufferers who had been injected with the vaccine containing squalene.

The Pentagon never told Congress about the more than 20,000 hospitalizations involving troops who took the anthrax vaccine from 1998 through 2000, despite repeated promises that such cases would be publicly disclosed. Instead, generals and Defense Department officials claimed that fewer than 100 people were hospitalized or became seriously ill after receiving the shot, according to an investigation by the Daily Press of Newport News.
A study conducted at Tulane Medical School and published in the February 2000 issue of Experimental Molecular Pathology included these stunning statistics:
“ … the substantial majority (95%) of overtly ill deployed GWS patients had antibodies to squalene. All (100%) GWS patients immunized for service in Desert Shield/Desert Storm who did not deploy, but had the same signs and symptoms as those who did deploy, had antibodies to squalene.

In contrast, none (0%) of the deployed Persian Gulf veterans not showing signs and symptoms of GWS have antibodies to squalene. Neither patients with idiopathic autoimmune disease nor healthy controls had detectable serum antibodies to squalene. The majority of symptomatic GWS patients had serum antibodies to squalene.”

According to Dr. Viera Scheibner, Ph.D., a former principle research scientist for the government of Australia:
“… this adjuvant [squalene] contributed to the cascade of reactions called “Gulf War Syndrome,” documented in the soldiers involved in the Gulf War.

The symptoms they developed included arthritis, fibromyalgia, lymphadenopathy, rashes, photosensitive rashes, malar rashes, chronic fatigue, chronic headaches, abnormal body hair loss, non-healing skin lesions, aphthous ulcers, dizziness, weakness, memory loss, seizures, mood changes, neuropsychiatric problems, anti-thyroid effects, anaemia, elevated ESR (erythrocyte sedimentation rate), systemic lupus erythematosus, multiple sclerosis, ALS (amyotrophic lateral sclerosis), Raynaud’s phenomenon, Sjorgren’s syndrome, chronic diarrhoea, night sweats and low-grade fevers.”

Clearly bypassing the FDA requirements for safety testing of these new adjuvants and the vaccines which contain them puts the entire population at risk for serious, possibly life threatening side effects, particularly any of the 12,000 trial paid trial participants (6,000 children) who are unfortunate enough to be randomized into the adjuvant containing groups.

Still, on July 23, 2009, the FDA announced, “Currently, no U.S. licensed vaccine contains the adjuvants MF-59 or ASO3. It is expected that a novel influenza A (H1N1) vaccine manufactured using the same process as U.S. licensed seasonal inactivated influenza vaccine but administered with MF-59 or ASO3 will be authorized for emergency use only.”

And that, “Two of the manufacturers (Novartis and GSK) have proprietary oil-in-water adjuvants (MF-59 and ASO3, respectively) which have been evaluated in a number of clinical studies including studies with influenza vaccines. These manufacturers will include an evaluation of the utility of the adjuvant for dose sparing and enhanced immunogenicity in their clinical studies. While there may be exceptions, in general, studies which include an adjuvanted arm(s) to evaluate dose sparing and enhanced immunogenicity may be conducted concurrently in the adult and pediatric age groups in order to have timely immunogenicity results to guide pediatric dose recommendations.”

The same document indicates that vaccines containing the un-approved adjuvants will be given to 100 children 6 months to 3 years old, 100 children 3 years old to 8 years, 100 individuals 18 to 64 years old and 100 individuals 65 and older in each of the multiple clinical trials. In addition, 700 individuals in each trial will be given non-adjuvanted vaccine.

Since the government has recruited 12,000 paid “volunteers” for the trials, it would be possible that as many as 10 trials could be conducted simultaneously.

Oddly, 60% of the world’s confirmed cases have occurred in people age 18 or younger, yet this age group (between 8 and 18) have been excluded from the clinical trials, with the results for this age group to be extrapolated from the other study data.
Given the fact the U.S. currently owns 268 million doses of the non-approved, non FDA tested adjuvant, the vaccines that contain this novel chemical will likely be found to be completely safe in these industry run trials. Unfortunately, the effects on the soldiers that experienced injury sometimes appeared long after the planned duration of the current trials.

*$5.6 billion in funding occurred in 2006 alone. The $5.6 billion spent for vaccine development in 2006 is 100 times the $515 million the FDA spent in 2006 for all FDA activity related to drug safety and efficacy for the entire drug industry including: pre and post approval testing, approval and regulation of over-the-counter and prescription drugs, biological therapeutics and generic drugs and personal care products such as fluoride toothpaste, antiperspirants, dandruff shampoos and sunscreens, monitor the more than 10,000 drugs on the market to be sure they continue to meet the highest standards, monitor TV, radio, and print drug ads to ensure they are truthful and balanced and provide health professionals and consumers information to use drugs appropriately and safely.

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VACCINE-A

“A shocking expose’ of experimenting with anthrax vaccine on unsuspecting members of the military. Investigative journalism at its best. A must read for any concerned citizen.”
---James C. Goodale, former Vice Chairman, The New York Times.

This is a book that the U.S. Department of Defense does not want you to read. It is about human medical experimentation—not that undertaken by the Japanese and Nazi doctors of World War II more than sixty years ago, but human experimentation being conducted on U.S. citizens by U.S. doctors and scientists working for the U.S. military. You may be familiar with some of the more shameful medical episodes in American history—the Tuskegee syphilis trials conducted by the U.S. Public Health Service or the Cold War LSD experiments conducted by the CIA. But this book is not about the past, except as the past is also prologue to our present and future. The unethical experiments detailed in this book are ongoing, with little prospect of being self-limiting. Why? Because they have been shielded from scrutiny and public accountability by national security concerns.

The victims of this story are the young men and women who volunteered for the U.S. armed forces, fully recognizing that they might be asked to risk their lives in battle and found themselves, without their knowledge or permission, the subjects of dangerous medical experimentation. Clinical evidence now exists that military doctors in both the United States and Britain have been testing a new anthrax vaccine on soldiers who weren't told they were getting an unlicensed immunization, let alone one that contains a substance shown in peer-reviewed scientific literature to be capable of causing incurable if not fatal disease. The justification for this secret experimentation was intelligence that Saddam Hussein had biological weapons that he might use if the war went against him. While Saddam had plans, if not an ongoing program, to develop a nuclear weapon, and certainly once had and indeed used chemical weapons, a sad irony of this story is that after years of U.N. inspections and now a war that has put Saddam Hussein behind bars, no samples of Iraqi dried anthrax have yet been discovered.

Following its stellar performance in the first Gulf War, the Afghan invasion and second war against Iraq, our nation's military establishment reached a level of popularity unseen since the years following World War II, in the process acquiring—the Abu Ghraib prison scandal aside—a patina of infallibility. This book will argue that the military has used public goodwill to shut off debate on a matter of vital interest to all Americans. I will show what can happen when the military is allowed to fend off criticism with national security claims and by equating criticism with disloyalty. Like any institution, the Department of Defense is as flawed and fallible as the humans who fill its ranks, and so the public must not assume that the DOD will always act honorably and with integrity because humans do not. Some will say that such talk is un-American. But I maintain that dissent against the abuse of power is one of this country's proudest traditions. It is a privilege that Americans have given their lives for, and one that we neglect at our own peril.

In 1990, when the United States launched Operation Desert Shield and then Desert Storm, I was an NBC correspondent covering the war from Saudi Arabia. Although the term was not yet used, I would become an embedded journalist for the ground offensive. Like the soldiers I covered, I was fully warned about the risk that the other side might employ biological or chemical warfare weapons. I had my protective gear and pills to take in the event of a nerve agent gas attack.

Fortunately, we won that war rather quickly. The air assault took little more than a month and the ground war ended in just four days. The Iraqi troops were simply no match for U.S. military power, and the "Mother of All Battles" that Saddam Hussein had threatened never materialized. As a result, American casualties were phenomenally low in comparison to those suffered in any other war in U.S. history. Sadly, many of the casualties that did occur were the result of friendly fire—we mistakenly hurt our own. But Saddam never put his dreaded biological and chemical weapons into play.

A little more than a year or so after war's end, reports began to emerge about a strange malady afflicting returning veterans. The symptoms were often vague, many subjective, but remarkably consistent—aching joints and muscles, rashes, fatigue, weight loss, weight gain, hair loss, sore gums, diarrhea, nausea, swelling of hands and feet, short-term memory loss and headaches. Of course, taken individually, these symptoms could each be attributed to a myriad of possible causes. Yet even grouped together they still did not add up to a recognizable disease, according to military doctors.

When people are scared, or in pain, as these GIs clearly were, when everyone is wondering who will be the next to be robbed of his or her meaningful life by crippling illness, rumors invariably abound. Because I am not, by temperament or training, the type of person to be caught up in idle rumor, my attention was caught not by the rumors themselves but by the military response to one of them, that a nerve agent might be the source of these complaints. Around 1997, the CIA and the military suggested a scenario that seemed to confirm these suspicions. It allowed for possible injury to about 100,000 troops, by remarkable coincidence almost precisely the number of Gulf War veterans who were registered as ill at the time.

The scenario went as follows: A U.S. Army engineering battalion inadvertently released a plume of nerve agent when it blew up an Iraqi ammunition at a place called Khamisiyah stocked with chemical munitions. If you read between the lines the subtext was clear: it was really Saddam's fault; he should not have been storing nerve agent. All this sounded quite plausible, except to those of us the military had trained to identify a chemical attack. The consequences we had been taught to look for in no way matched the symptoms the sick GIs were experiencing.

The military's own scientific literature—research with nerve agents tested on both animals and humans and published decades earlier—also undermined the idea that nerve agents released into the open air could cause the symptoms Gulf War veterans were reporting. Eventually, the military's own epidemiologists published data that further discredited the nerve agent theory, and angry senators censured both the Army and the CIA for releasing highly speculative, spurious information. The GAO has recently published a report saying there was no sound basis for the Khamisiyah theory.

But by that time, I had other reasons to see the nerve agent explanation as untenable. I strongly suspected that Gulf War Syndrome was not caused by something that had happened in Kuwait or Iraq. Why? Because soldiers from most of the countries in the anti-Iraq coalition did not suffer from this malady. No Arab soldiers or civilians, on either side, got sick. Nor did any journalists get sick, embedded or otherwise. Of all those who had been on the ground during the war, only soldiers from the United States, Great Britain, Canada and Australia were experiencing symptoms. Also telling was that GIs who had never left these shores were complaining of the same symptoms as those who had been deployed to the Gulf.

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The more I thought about the nerve agent explanation, the more I wondered why the CIA and the Army would have propagated an explanation that would in time surely come to be revealed as bogus and thereby subject them to justly deserved ridicule. What were they hiding that was so uncomfortable that they put out such a manifestly unsupportable explanation? Or were they hiding nothing? Was I just missing something? My own first reaction was to assume that I had indeed missed something.

I am someone who had three uncles who served proudly in the U.S. Army—two of them were sergeants and the third retired a lieutenant colonel. My dad was a buck private too young to see combat in World War II, but he went through boot camp and did his tour of duty in Tennessee at the end of the war. I looked up to these men, in part, because they had served in the Army. As a young Japanese-American growing up in the 1950s, I played war, as young boys invariably do, even when the neighborhood kids taunted me about being a Jap. But I knew—even if they didn't—that one of the most decorated combat units in U.S. history was a band of "Buddha-heads" made up of Hawaiians of Japanese descent and volunteers out of the relocation camps for Japanese-Americans on the mainland—all American-born—who fought with valor in Europe. Still later, I learned about those colorful characters in the Pacific—guys like my cigar-chomping Uncle Thomas—who served in military intelligence as a translator. I heard less from my Uncle George, who served on the front lines in Korea as a sergeant in the Army Signal Corps; Uncle George lost so many of his friends in that war that he never wanted to talk about it. From his reticence I gathered that war was not quite the bloodless affair I saw on my favorite '60s TV show, Combat, though as a young boy I could not even begin to conceive its true carnage. It was my Uncle Shug—a lieutenant colonel in the military police who served as an Army criminal investigator in occupied Japan and then in Germany—who used to tell me with conviction that in the Army there was only one color: olive green.

With a 1-A classification and a low draft number, I was a prime candidate for the rice paddies of Vietnam, but President Nixon ended the draft just as I was about to be called up. Instead, I spent two years in a mandatory Army ROTC program at a religious college I attended outside of Chicago—a college that graduated at least one speechwriter for the current Bush administration. I come from a Midwest Republican family whose members are "born again" Christians. While I don't claim to be exactly like my family in dogma or politics (who is?), I am proud of my heritage, particularly of my family's service in the Army. As a TV journalist I sought out assignments involving the military whenever I could, and won awards for my reporting.

I have gone on at some length about myself because what I am about to relate in this book is more than a controversial story. It is an almost unbelievable story. All told it took me six years to pull all the pieces together. But once I felt I knew what had happened and why, I had only one goal in mind—to draw attention to the secret activities of a few (not all) U.S. military doctors, who, I came to realize, have been medically experimenting on troops for the past fifty years, almost without pause. There is clinical evidence that their most recent experiment led to an unknown number of formerly healthy young men and women—possibly tens of thousands of them—having their lives destroyed by illness. Some have even died.
This book will show that shortly after the war ended, the U.S. government, in response to the catastrophic nature of Gulf War illness, spent well in excess of $100 million on studies to learn what the illness was and what had caused it. These studies came to the conclusion that no single disease could account for all the medical problems experienced by sick Gulf War veterans. The degree of illness from one to the next veteran varied enormously—from aches and pains to death. U.S. military doctors used these studies to justify treating Gulf War veterans complaining of these symptoms as if they were suffering from nothing more than psychosomatic illnesses due to stress, denying them modern medical treatment.

I will then tell you about a researcher and her husband, a physician, and finally other scientists at Tulane University, who identified the symptoms experienced by Gulf War veterans in their study as autoimmune. What is autoimmune disease? It is the damage that occurs when the immune system mistakenly identifies the body's own tissues as foreign matter and then attacks it. Lupus, rheumatoid arthritis and multiple sclerosis—diseases that the anthrax vaccine manufacturer openly associates with its vaccine—are all autoimmune. Upon examination by civilian doctors, some veterans—said to be suffering from an indefinable syndrome—were diagnosed with autoimmune diseases. Most important, I will show that Tulane helped establish one of the most important and painful pieces of information—that these illnesses were iatrogenic, that is, induced by medical treatment.

By developing an assay—a test to determine whether an individual has antibodies to a particular substance in his or her blood—scientists from Tulane University Medical School established what they say is a "marker" for Gulf War Syndrome. This marker identifies whether a GI had been injected with a substance called "squalene" (pronounced SKWAY-leen). Those who had a so-called Gulf War illness consistently tested positive for antibodies to squalene in their blood; healthy Gulf War veterans do not have these antibodies. The Tulane scientists then tested their next hypothesis—that squalene had been introduced into these veterans through the anthrax vaccine the veterans had been given. The licensed anthrax vaccine, they knew, did not contain squalene, which explains why hundreds of thousands of soldiers did not get sick. To test the connection between Gulf War illness and a possible, unlicensed, experimental anthrax vaccine secretly given to an unknown number of military personnel, Tulane tested the blood of four Air Force reservists scheduled to get their anthrax vaccine. Before the vaccination, their blood did not contain the antibodies. Afterward, it did. All four had been injected with anthrax vaccine confirmed by the FDA to contain squalene.

Squalene is what is called an adjuvant. Adjuvants stimulate the immune system to respond—which is what a vaccine has to do to build up immunity. My book will show why the military doctors felt they needed an immuno-stimulant so desperately just as the Gulf War began—their licensed vaccine was not going to be effective quickly enough. It can take weeks to develop immunity with a good vaccine; with the licensed anthrax vaccine, a not-so-good vaccine, it can take months. When military doctors started vaccinating troops less than ten days before the United States would be at war, it was almost pointless to use the old vaccine. Using the Army's newest anthrax vaccines was the logical thing to do. At the time, Army scientists believed that they could generate more immunity in less time with just one shot of the new vaccine. Had Saddam launched an attack with anthrax resulting in mass casualties, not using this new vaccine would have been seen, in retrospect, as a near dereliction of duty.

There was little downside to such a decision. Army scientists thought their new vaccine was safe. Sadly, as the clinical evidence now attests, U.S. and British military personnel paid a terrible price for this mistake, a mistake that might not have been made had the Army scientists been more familiar with the literature on oil-based adjuvants.

Rather than defend their actions as a hard judgment call, to this day, military doctors deny having used an experimental anthrax vaccine and deny that the anthrax vaccine given any veteran had squalene in it.

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CHAPTER 3

The Greatest Story Never Told

For the past 17 years, the Army has been working on a new anthrax vaccine that contains no anthrax, and is made with an ingredient that it does not want to name. That ingredient is called squalene. Squalene is an oil. Without it, the new vaccine will not work any better than the old one. In fact, for all intents and purposes, without squalene the new vaccine is the old one. What makes squalene so important is its proven ability to stimulate a strong response from the immune system. That is something the main ingredient of the new vaccine, the now ultra-purified protein secreted by the anthrax microbe—recombinant protective antigen—cannot do by itself. It is too weak.

Immunologists have a special name for substances used to boost feeble vaccines. They are called adjuvants. Adjuvants are arguably the most extensively researched pharmaceutical product in the last quarter century that you never heard of. I have used the word adjuvant three times in this paragraph so far and that is probably three times more than you have ever seen it in print before. This is partly because the most effective adjuvants, those formulated with oils, are too dangerous for human use. That is squalene's other proven ability, causing incurable disease, which is why it is such a touchy subject with the Department of Defense.

The word adjuvant comes from a Latin word that means "to help." But with oil adjuvants like squalene that term is misleading. Today, only one adjuvant—an aluminum salt called alum—is licensed for human use. All the oil adjuvants are so noxious that their use is restricted to experiments with animals, and even then, governments have written strict regulations to govern how they are used. The classic oil adjuvant, called Freund's Complete Adjuvant, is considered too inhumane to even inject into animals. It does a terrific job of stimulating the immune system, though. Unfortunately, Freund's Complete Adjuvant can cause permanent organ damage and incurable disease. As early as the 1930s, these oil additives were notorious for inducing illness. By the 1950s, scientists knew these illnesses were specifically autoimmune. Today that is their chief use in research—inducing disease instead of preventing it. Scientists studying autoimmune disease cannot wait around for its spontaneous appearance in a lab animal; they inject it with Freund's Complete Adjuvant to reproduce autoimmunity on demand. Oil adjuvants made with squalene equally effective at this job, and regrettably according to Dutch scientists, equally inhumane.

Autoimmune diseases are chronic and progressively debilitating ailments; some, like multiple sclerosis and lupus, can be fatal. They occur when the immune system loses its ability to distinguish what is "self" from what is foreign. Under normal circumstances, your immune system ignores the constituents of your own body; immunologists call this "tolerance." But if tolerance is broken, the immune system turns relentlessly self-destructive, attacking the body it is supposed to defend.
Adjuvants can break tolerance. In 1956, Dr. Jules Freund, the Hungarian born scientist who gave his name to the adjuvant he created, warned that animals injected with Freund's developed terrible conditions: allergic aspermatogenesis (stoppage of sperm production), experimental allergic encephalomyelitis (the animal version of multiple sclerosis) and allergic neuritis (inflammation of nerves that can lead to paralysis), allergic uveitis (an inflammation in the eye that can cause blindness). There was no reversing any of these conditions.

Scientists are still unsure why oil adjuvants do this. One theory is that oils have the ability to hyperactivate the immune system. "The cause is probably that when injecting these molecules, you create a chaos in the immune system," says Dr. Johnny C. Lorentzen, and immunologist with the Karolinska Institute, which awards the annual Nobel Prize for Medicine. He says these oils induce "an extremely powerful response," so powerful, in fact, that the immune system goes haywire and starts attacking things it would otherwise leave alone. Another possibility, which has not been explored very much, is that this harmful phenomenon actually has something to do with one of the greatest distinguishing characteristics of the immune system—its specificity. Over eons in time, this extraordinarily elegant and powerful system has evolved to respond very precisely to what it deems potentially harmful to the body. Our bodies contain all sorts of oily molecules. It could be that when an oil is injected, the immune system actually responds to it with a high degree of precision - just as it responds to everything else - but because the adjuvant resembles too closely those oils found in the body, the immune system begins attacking those too. In immunology this is called a "cross reaction." Neither proposition - chaos or specificity - has been proven so far. But however oils do their damage, it is well known that they do.

Army scientists have been as aware as anyone else of the harm that injecting oils can do. The problem for military personnel is that these scientists learned this lesson by injecting oils into troops in experiments that in some cases they did not agree to participate in. The central question in this book is whether such an experiment has been done again with the new anthrax vaccine and squalene.

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Round One

Despite their dangers, oil adjuvants have come to exert an irresistible, almost magical allure on researchers. If they could truly stimulate the immune system safely, oil additives could help defend mankind from diseases like malaria and HIV. For germs such as these, no one dared make a classic vaccine - the kind made from the germ itself - for fear of accidentally infecting someone with an incurable, if not fatal infection. By splicing off just little bit of such a germ - not enough to make anyone sick - and combining that shard with an adjuvant, scientists hoped to protect people from lethal microbes. If they could do it for HIV, they reasoned, they could do it for any germ in creation. This siren song was so powerful that it did more than induce researchers to indulge in cynical risk/benefit calculations; in some cases, it made them forget the risks altogether.

The first time Army scientists succumbed to this allure was in 1951 at Fort Dix, New Jersey in an experiment that involved 44,459 troops. More than 18,000 of them got injected without their informed consent with a newly formulated oil additive for vaccines. The Army thought it had something new and safe. The world's best additive that no one dared inject into humans, Freund's Complete Adjuvant, was more than just mineral oil. It also contained Mycobacterium tuberculosis, the germ that caused TB. The mycobacteria were dead, but scientists thought they still might be in some way responsible for the problems associated with this concoction. So they removed the mycobacteria in hopes that the oil alone could do the trick; they called this new adjuvant "Freund's Incomplete Adjuvant." The incomplete adjuvant was just mineral oil in water, and a detergent to keep the oil evenly dispersed. Using it was a risky thing to do, but the Army considered the risks of not running this experiment even higher. This "incomplete" additive had been incorporated into an experimental flu vaccine. It was the flu that really worried the Army.

By all accounts, the great Spanish Flu pandemic of 1918 wasn't really Spanish at all. It was American. In fact, it was an Army flu. The first victim, the "index patient," was an Army private named Albert Gitchell who worked as a cook at the Army's Camp Funston on the vast Fort Riley military reservation in Kansas. It is believed that U.S. troops heading to Europe brought this flu with them. Before it was over, more than 20 people had died of influenza around the world—the deadliest natural disaster in world history.

Army scientists wanted to prevent another global killer from emerging from an Army post where new recruits might become an unintended hatchery for some vicious new flu strain that once again could wipe out millions of people. Trying out a new oil additive on troops seemed like a relatively modest risk in comparison to the benefits of a better flu vaccine.

The Fort Dix experiment took place with the blessing of Fort Detrick. It was funded by the U.S. Army Medical Research and Development Command (USAMRDC), which would later oversee the development of the new anthrax vaccine and newer oil additives too. The Armed Forces Epidemiological Board (AFEB), which would be sponsor a large number of the experiments conducted on military personnel, would later recommend the injecting an experimental flu vaccine containing oil into every man and woman in the U.S. military without their informed consent. The risk of an outbreak of killer flu seemed too great to do otherwise. To run this experiment, the Army would contract none other than Jonas Salk. Salk had already tested Freund's Incomplete Adjuvant on medical students at the University of Pittsburgh under the sponsorship of the Armed Forces Epidemiological Board, and with funding from the Army Surgeon General. Based on this study, Salk thought it was safe.

Over the next two decades, the entire U.S. public health establishment - civilian and military - kept watch on what happened to the troops from Fort Dix. Everyone wanted in on the act. USAMRDC funded this study and its follow-ups. The National Academy of Sciences, the Walter Reed Army Institute of Research (WRAIR) and the Walter Reed Army Medical Center (WRAMC) did the initial round of surveys. Then the list started to grow. The National Academy of Sciences and the National Research Council organized more studies at the request of the Veteran's Administration, the Army and the U.S. Public Health Service "in collaboration with the Armed Forces Epidemiological Board." At the 17-year mark, academia got involved too. An AFEB scientist on the faculty of the University of Michigan School of Public Health organized yet another follow-up. No one, it seemed, wanted to be left out of such an important experiment.

And the experiment that seemingly had no end. Twenty-one years after Salk first injected unsuspecting soldiers with a theoretically new and improved flu vaccine, the Fort Dix troops were under the microscope yet again. The list of sponsors included many of America's most respected public health institutions: the National Academy of Sciences-National Research Council, the American Cancer Society, the Veterans Administration, the Department of Defense, the U.S. Public Health Service and the Commission on Influenza of the Armed forces Epidemiological Board. USAMRDC bankrolled this study, just as it did the first one. What was remarkable about this 21-year project - involving the military, civilian public health authorities and a major university - is that at no time during its execution did any of the scientists involved publicly discuss whether it was ethical to run a medical experiment on people without telling them. If these doctors had any concerns, they did not publish them.

Long before the last study was completed, AFEB proposed the adoption of an experimental flu vaccine with oil for everyone in the military. In 1963 and 1964, AFEB recommended injecting every man and woman in the armed forces with the new vaccine. The board also recommended that Department of Defense also commence studies with oil added to tetanus and diphtheria toxoids, and polio vaccines. , Army doctors seemed determined to add oil to every vaccine they could.

Here is what they were not telling anybody. By 1964, the year when everyone in the military was supposed to get immunized with an oil-boosted influenza vaccine, the Army already knew the risks this vaccine presented for a very specific type of illness. AFEB's Colonel Abram S. Benenson had drawn up a list of diseases that investigators should watch out for in veterans injected with the oily flu vaccine at Fort Dix. Benenson's list read like the contents of a chapter on autoimmune disease in an immunology textbook. It included multiple sclerosis, myelitis, Guillain-Barré syndrome, uveitis, neurodermatitis circumscripta and disseminata, amyloidosis, lupus erythematosus, dematomyositis, scleroderma, chronic pericarditis, Raynaud's disease, rheumatoid arthritis, rheumatoid myositis and acute glomerulonephritis—all of them autoimmune diseases.

The final study on the Fort Dix troopers had data that none of the previous ones had: autopsy results. The soldiers had grown older and many of them had died. Epidemiologists, mainly working for the National Research Council and the American Cancer Society, reported a "significant excess of deaths" in soldiers given the oil-boosted vaccine, which the investigators related to "ill-defined vascular lesions of the central nervous system." They attributed this fact to the greater number of autopsies available for the soldiers given the oil-boosted vaccine. But there were hints of a problem with autoimmunity. Ten percent of the soldiers studied, who were injected with the oil-boosted vaccine, developed a "collagen disease," which is a term doctors used to use interchangeably with autoimmune disease. Still, the number of patients in this study was too low to extrapolate any reliable conclusions from the data. That did not prevent government and military doctors from doing just that. They concluded that the oily flu vaccine was safe. Nevertheless, what the government then did not do was telling. The FDA never licensed the vaccine, or the oil adjuvant, for human use.

The Fort Dix experiment was the first time Army doctors and scientists injected an oil-boosted vaccine into U.S. troops without informed consent; there is now clinical evidence that it was far from the last. For more than a half century, factions in military medicine and in the U.S. public health establishment have actively campaigned to get an oily vaccine additive licensed, seemingly at any cost.

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The Emperor's New Clothes

When scientists at Fort Detrick, following Joe Jemski's 1992 talk, reviewed the existing literature on the Wright vaccine, it didn't look good. Even with 6 shots, the vaccine did not protect very well. Guinea pigs vaccinated with the licensed human vaccine died when exposed to certain strains of anthrax. In 1986 the bad news got worse. In discovering that the licensed vaccine protected against the Army's old weapons strain, Vollum - from which the vaccine had been derived - Stephen Little and Gregory Knudson also discovered 8 more anthrax strains for which the PA vaccine did not work. Among them was the now notorious Ames strain that was mailed in 2001 anthrax letter attacks. Like the Army's previous research, the data confirmed that a live spore vaccine provided better protection against more strains. "The fact that the spore vaccine provided protection against all isolates tested suggests that other antigens may play a role in active immunity," they concluded. Which would argue for a live anthrax vaccine, but Fort Detrick's scientists expressed an age old concern about problem with living vaccines that could be traced all the way back to Pasteur: "Since this vaccine is a live immunogen," they warned, "safety factors must be considered before its use." Little and Knudson did not rule out the possibility of resorting to a live spore vaccine, but that is not what they then chose to pursue.

When they, along with Fort Detrick scientists Bruce Ivins and Sue Welkos, began working on a new anthrax vaccine, they chose a design that was all the rage at the NIH—subunit plus adjuvant. "Subunit" refers to small fragments of a germ. For safety, NIH scientists were using subunits of lethal viruses like HIV to be the chief component of their new generation of genetically engineered vaccines. These ultra-pure vaccines, which reduced an immunization to mere molecules from a microbe, were safe, but at a price. They were weak. In some cases, they afforded no detectable level of protection at all. This is why the NIH wanted an adjuvant more robust than alum for its new vaccines.

The subunit that Little, Knudson, Ivins and Welkos chose for the Army's new anthrax vaccine was a little surprising. It was protective antigen—the same main ingredient in the vaccine they were trying to replace. Although all the data from both U.S. and British military experiments from the 60's forward indicated that more components of the anthrax microbe needed to be in any effective anthrax vaccine—a fact that even Little and Knudson acknowledge in their 1986 paper—Fort Detrick's newest generation of anthrax investigators did just the opposite. In fact, they did one better. With recombinant DNA technology, their new vaccine would eliminate every extra molecule of anthrax unrelated to protective antigen. It would be purest PA formulation ever made, and would hence be the weakest anthrax vaccine ever made. Remember, in immunology, purity equals weakness.
Yet when Fort Detrick's scientists traveled to England in 1989 to report on their new vaccine to the International Workshop on Anthrax, they had some startling results to announce: Fort Detrick had found what everyone had been looking for: a single-shot anthrax vaccine. In guinea pigs, the new anthrax vaccine produced complete protection against the Ames strain with just one dose.

If this was completely at odds with everything Army scientists had found over the previous three decades, it was because the Fort Detrick team had added something new to the formula. It was a kind of trick, though not in the sense of something fraudulent or deceptive. The Army's scientists made no effort to conceal what they did. Quite the contrary, they reported this trick in great detail. It was an old trick. In the 80s, scientists at NIH had been promoting the use of oils in vaccines again. By now, there was a new crop of oily vaccine boosters hot off the lab bench. It was the oil emulsions that helped transform the Army's hapless protective antigen formula into a potent single-shot vaccine.

Dr. Bruce Ivins informed the workshop gathering in old cathedral city of Winchester that he had added three different adjuvants to his one-shot wonders. One was called "Tri-Mix," another "DeTox," and a third was "SAF-1," which stood for Syntex Adjuvant Formula I. They were all made with bacterial scraps from truly noxious microbes like Salmonella typhimurium and Mycobacteria tuberculosis. The British scientists from Porton Down tried a different tack—adding a preparation to the British anthrax vaccine made from the whooping cough germ, Bordetella pertussis. At Winchester, the Porton contingent called their approach "microbial supplementation." All of these adjuvants relied on bacteria, or portions of them, to stimulate the immune system.

The three additives used by Fort Detrick, however, differed from Porton Down's in one very significant way. The Fort Detrick additives were all emulsified in oil. The oils were only supposed to be "vehicles" that conveyed the bits of bacteria through the bloodstream. SAF-I, which provided less protection than the other two, contained the oil squalane. The two adjuvants that helped provide complete protection from Ames in guinea pigs, Tri-Mix and DeTox, were emulsified in squalene. At the time, no one at Fort Detrick or the NIH seems to have been aware that these oils were themselves immunostimulants.

Having invested decades into refining protective antigen to a singular purity, Ivins et al. were essentially polluting this new ultra-pure vaccine with extraneous antigens to make it work. That is what an adjuvant was—extra antigenic material for a vaccine that had been purified to such an extent that it could no longer do the job it was designed to do. Perhaps it was the importance of their apparent breakthrough that blinded these scientists to what they had done. Whatever it was, it prevented them from seeing the absurdity of their new creation, or its risks. A fully intact microbe presents dozens of different chemical binding sites an antibody can latch onto. Each of these sites is a separate target for a multi-front attack by the immune system. In pursuit of purity, Army scientists had removed all of the targets of anthrax germ but one. Now they had a dubious product that they were determined to improve, and they did it by adding targets from germs other than B. anthracis. Instead of adding more antigenic material from the anthrax microbe - as Lincoln had suggested in the 60s and as Turnbull and Melling had done in the 80s—the Fort Detrick team incorporated pieces of completely different germs.

This was Rube Goldberg immunology. The Army's vaccine whiz kids had devised the most convoluted, expensive and time-consuming way conceivable to make a virtually identical product—protective antigen—and then added material that essentially diverted the immune system's attention away to antigens unrelated to anthrax. Fort Detrick's new, souped-up single protein vaccine, like the old one, did nothing to induce an immune response to the organism itself, which could still feed, secrete toxins and multiply inside a vaccinated host. There was also one more flaw in this design: oils are potentially toxic, and the Fort Detrick team knew it. In Bruce Ivins' frequently cited paper on the Army's pursuit of an improved human anthrax vaccine, he noted that oil adjuvants "can provoke toxic, allergic, ulcerative, or lethal reactions." This should have prevented him from committing Fort Detrick to an oil-boosted anthrax vaccine in the first place, but for reasons that Ivins has never publicly disclosed, it did not deter him. Neither he nor anyone else who worked on this vaccine at Fort Detrick has published an explanation for why they did this.

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Round Two

Anyone even remotely familiar with oil additives for vaccines could have told you that they were a big problem. For reasons science has yet to fully explain, oils and other fatty substances found in the body, like cholesterol and phosopholipids, are potent stimulants to the immune system. Try as they might, scientists trying to harness this property have yet to come up with an oil adjuvant safe enough to use in humans. Since the 1930's, the gold standard has been the aforementioned Freund's Complete Adjuvant—an elixir banned from human use because of its toxicity. When Freund's Incomplete Adjuvant, a vaccine additive made chiefly from mineral oil, proved too risky as well, scientists tried changing the oil.

In the early 1970s, scientists at UCLA Medical Center, including one of the most respected rheumatologists in the country at the time, Carl M. Pearson, started looking for a less toxic alternative to Freund's. They ran a series of experiments with a variety of edible oils on the assumption that because they were "metabolizable" the body could process them safely. In other words, if you could ingest them, you could inject them. Intuitively, this premise seems somewhat dubious: your body could metabolize a cheeseburger, for instance, but you couldn't liquefy it in a blender and inject the resulting slurry, and then expect to feel well in the morning. Pearson's associates, Michael Whitehouse and Frances W. Beck, injected more than dozen of these metabolizable oils into rats, including castor oil, coconut oil, olive oil, sesame seed oil, cottonseed oil, corn oil, wheat germ oil, safflower oil, cod liver oil, oleomargarine, and the commercial lubricating oil, silicone. When these were mixed with heat-killed Mycobacteria tuberculosis, the UCLA group got results it didn't expect. All of the oils were toxic; they all induced arthritis in rats with varying degrees of severity. The data changed Whitehouse's views on the safety of metabolizable oils. "To summarize very simply, I think most oils are dangerous," he now says. Based on their ability to cause arthritis, the researchers assigned the oils "arthritis scores," ranging from (+), which was moderately toxic, to (++++), which was guaranteed to cripple. Of all the metabolizable oils tested by Pearson's group, two were better than all the others at causing arthritis: squalene and squalane, the same emulsifying oils that Bruce Ivins used in his single shot anthrax vaccines.

Squalene and squalane scored (+++) and (++++) respectively. Between these two oils, squalene is the one you could definitely eat. Olive oil contains squalene; in theory, you could drizzle it onto a salad along with a little vinegar and have no worries. Your body would metabolize it along with the arugula and endive without as much as a hiccup. Injecting squalene, though, was another story. To make sure it was the oils that did the damage, Beck, Whitehouse and Pearson tried injecting rats with squalene and squalane without mycobacteria in the formula. Rats injected with either squalene or squalane all developed experimental allergic encephalomyelitis—the same MS-like disease caused by Freund's. The injected animals were left hobbled, dragging their paralyzed hindquarters through the wood chips in their cages. , The UCLA team had found what it was looking for: oils that induced autoimmune disease, but with less inflammation. Between the two of them, squalene was less desirable for UCLA's purposes. "Squalene was more arthritogenic," Beck recalls, "but it also produced a greater inflammation."

Risk v. Benefit

Given these oils proven ability to induce autoimmune disease, the Army's decision to put either of them in its second generation anthrax vaccine only makes sense when you put it in the context of the times, and in this case, a specific location. When he cancelled America's offensive biological warfare program, President Nixon also freed up some building for a more popular research effort. Arriving by helicopter at Fort Detrick's Blue and Grey Field in October 1971, President Nixon personally announced the creation of the Frederick Cancer Research Facility of the National Cancer Institute (NCI). Nixon had Fort Detrick allocate about 68 acres and 70 of its buildings as a new research campus for NCI. It was a fateful decision that would have consequences that even a president as forward-thinking as Nixon could not have foreseen. It would set in motion a series of decisions that would lead, almost inevitably, to the use of a substance that would endanger the health of hundreds of thousands of U.S. troops.

It is unclear how squalene first came to the attention of Army scientists at Fort Detrick, but one possibility is through the National Cancer Institute, now on its doorstep. Eliyahu Yarkoni and Herbert Rapp of NCI published a paper in 1979 that stirred national and international interest in the alleged therapeutic benefits of squalene and squalane. When combined with fragments of a particular bacterium, squalene and squalane had an astonishing effect. Yarkoni and Rapp reported complete tumor regression in mice injected with squalane, and nearly complete regression (92%) in mice injected with squalene. When they injected these oils directly into mouse tumors, the tumors either shrank or disappeared completely. The more oil in the mixture, the better it worked. Based on these early experiments, oils looked like they might hold the keys to the kingdom—a cure for cancer. There was, however, a hitch.

Yarkoni and Rapp knew about the UCLA data; citing the Beck and Whitehouse paper, Yarkoni and Rapp reported that squalene and squalane both caused autoimmune disease in rats—a fact that you will not find mentioned in any Army paper concerning Fort Detrick's work with squalene emulsions in the new anthrax vaccine. Even Yarkoni and Rapp barely mentioned the problem with squalene and squalane; it was limited to a single sentence at the end of their short paper. Although causing debilitating and ultimately fatal neurological damage in animals was a big downside, their concern, after all, was cancer.

Several more factors emerged in the 1980s that would affect the direction of the Army's anthrax vaccine research. The first was HIV. After the discovery of the human immunodeficiency virus in 1984, the cause of Acquired Immune Deficiency Syndrome (AIDS), the National Institutes of Health would devote billions to develop a vaccine. That year, the Centers for Disease Control reported 7,699 AIDS cases with 3,665 dead. By 1988, the number of diagnosed U.S. cases was 82,764 with 46,344 dead. That was a jump of more than 1000% in just 4 years. Mortality was 100%; for someone with AIDS, drugs could prolong life but not save it. Public health officials doing the math were horrified. No one dared make a whole virus vaccine, living or dead, from a germ like HIV. Vaccine researchers embraced gene-splicing as their only alternative—inserting HIV genes into non-lethal organisms like vaccinia. But the results were disappointing: these microbial hybrids barely elicited an immune response. That's why a new adjuvant was essential to NIH. Because of Yarkoni and Rapp's work, squalene and squalane emulsions had by then established themselves as NIH's adjuvants of choice.

HIV was threatening to become the great plague of the 20th century, worse even than the flu pandemic of 1918 that claimed more than 20 million lives. It was the public health cause célèbre of the 1980s. Rock Hudson had it; so did Liberace. When an Indiana school banned 14 year-old Ryan White from classes because he had HIV, Elton John and Michael Jackson became his friends and offered their support. Vice-President George Bush called for mandatory HIV testing. No other disease made as many headlines or pushed as many political buttons. For NIH, that translated into wide open government coffers. For researchers, it offered a shot at immortality. Any scientist who found a way to stop this new global scourge could reserve a seat in Stockholm for a Nobel Prize ceremony. A successful recombinant HIV vaccine would be just a start. The goal was to roll back all infectious diseases through immunization if that were possible. But it wasn't going to happen without a more powerful vaccine booster. The FDA, stung by criticism from dying AIDS patients who wanted access to new drugs that could keep them alive even a few months longer, started to "fast-track" drugs through its licensing labyrinth, including experimental vaccines containing squalene. This was not without risks. The problem with the fast track was knowing when someone was playing it fast and loose.

Even NATO got on this bandwagon by sponsoring a conference in Cape Sounion, Greece, on vaccine adjuvants in the summer of 1988. The search for a new adjuvant was now a matter of national security. The U.S. Army sent a contingent from its Walter Reed Army Institute of Research led by Dr. Carl R. Alving, a proponent of vaccine boosters emulsified in squalene, in addition to his own favorite: liposomes. Liposomes are microscopic vesicles containing vaccine antigens. Think bath oil beads. Encapsulating bath oil in soluble beads makes it possible to transport measured doses of oil from the drug store where you bought them to where you ultimately want to put them—in your bathtub. Alving's liposomes were made from cholesterol, another oily substance closely related to squalene.

The Soviets Again

If anyone in the military had been inclined to ask questions about squalene's toxicity in the late 1980's, something else happened around that then that might have diverted them. In October 1989, a high-ranking Soviet biological weapons scientist defected to the West—the first one to do so. This was an extraordinary intelligence coup. At the invitation of a French pharmaceutical equipment maker, Dr. Vladimir Pasechnik of the Leningrad Institute of Ultra-Pure Biopreparations went to Paris for a conference and never went home. He left his family behind in Russia and wound up in Britain. One of the scientists who debriefed Pasechnik for the British was Jack Melling. "Pasechnik chose Britain," says Melling, "because he thought the U.S. still had an active biological warfare program and he didn't want anything more to do with making weapons. He didn't think the same of Britain." According to Melling, what Pasechnik told Britain's MI-6 raised even more alarm about the U.S. and British chemical anthrax vaccines. Pasechnik said that Moscow had created antibiotic-resistant super-strains of anthrax, plague and tularemia. Although Pasechnik's British handlers couldn't verify this, it sounded plausible enough to them; in part because making germs antibiotic-resistant was relatively easy to do, and in part because the Soviets had published several papers in the 1980's disclosing that they had developed a veterinary vaccine that immunized against all three of these microbes. Intelligence analysts had been asking themselves why Soviet livestock would need to be vaccinated against plague, tularemia and anthrax—the three agents regarded by bioweapons specialists as the most likely ones to be used in a biological warfare attack. They could not come up with a good answer.

Back in Maryland, Fort Detrick now had at least four viable prototypes of a single shot vaccine that they thought was safe. All were made from the protective antigen protein or pieces of it. Three others were recombinant vaccines; Fort Detrick had cloned the protective antigen gene into Bacillus subtilis, baculovirus and vaccinia. All of these prototypes were formulated with squalene or squalane. The ones showing the most promise were the protective antigen vaccines combined with these oils. According to Ivins and his Fort Detrick colleagues, just one dose of these new vaccines gave protection equivalent to three doses of the licensed U.S. vaccine and the new vaccines were ready for clinical trials. All Fort Detrick needed now was the right time and place to test them.

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Six pregnant women hospitalized

MONDAY, 03 JANUARY 2011 00:00
By Kanchan Kumara Ariyadasa

At least six pregnant women were hospitalized on Saturday two days after receiving the A/H1N1 vaccination at the Dambulla Hospital.

Relatives of the victims had charged that doctors had given expired A/H1N1 vaccination to these pregnant women.
However, officials of the Dambulla Medical Superintendent Office had told the relatives that they had not given any expired vaccination to them.

Medical Superintendent of the Dambulla Hospital Dr. Iqbal said that they had not given any outdated vaccines but still conducting inquiries to find out whether were any side effect had been caused due to the vaccination.

The health ministry last week instructed all pregnant women to get A/H1N1 vaccination with the increment of Swine Flu Island wide.

LINK: print.dailymirror.lk/news/front-page-news/31739.html

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Study: Swine Flu Vaccine Linked to Narcolepsy
Updated: 3 hrs ago

Last Updated On: 2/1/2011 5:39:33 PM

HELSINKI -- Finnish researchers have found an increased risk of narcolepsy among 4 to 19-year-olds who were given swine flu shots, a government health agency said Tuesday.

A preliminary study by the National Narcolepsy Task Force indicates that children vaccinated with Pandemrix "contributed to the observed increase in incidence of narcolepsy" compared to those who were not vaccinated in the same age group, it said.

The agency said, however, that the increase likely was caused "by joint effect of the vaccine and some other factor," and added that it would have to conduct more research as similar increases in narcolepsy cases have not been reported in other countries using the vaccine.

Pandemrix shots were made for the swine flu pandemic, and it is not clear how many people would still be receiving them since the usual flu shot now includes the swine flu strain. In Finland, health personnel stopped administering Pandemrix in August 2010 when concerns were first voiced about the vaccine.

Narcolepsy is a rare disorder that causes people to suddenly fall asleep. It is seldom fatal.

The Finnish National Institute for Health and Welfare, which published the findings, said that 60 children and adolescents contracted narcolepsy in Finland in 2009 and 2010. Fifty-two of them - or almost 90 percent - had received the Pandemrix vaccine, it added.

It's not clear how many in the young age group were vaccinated with Pandemrix but half of Finland's 5.3 million population were given the shot during the winter of 2009 to 2010.

"Based on the preliminary analyses, the risk of falling ill with narcolepsy among those vaccinated in the 4-19 years age group was nine-fold in comparison to those unvaccinated in the same age group," the study said.

It found that the biggest increase was among those aged 5 to 15 years. No cases were seen among those under age 4 or over age 19.

The European Medicines Agency, the regulatory body responsible for authorizing use of the vaccine, launched an investigation into a possible link between the swine flu vaccine and narcolepsy in August.

GlaxoSmithKline PLC, which produces Pandemrix, said it was aware of the Finnish report.

"This investigation is independent of a broader ongoing European Medicines Agency investigation initiated in 2010," the company said in a statement. "GlaxoSmithKline is reviewing the report and believes it would be premature to draw any conclusions on a potential association between Pandemrix and narcolepsy until this European investigation has been completed."

The company said that more than 31 million doses of Pandemrix had been administered in 47 countries with 162 cases of narcolepsy reported in people who were vaccinated. Some 70 percent of the cases originated in Finland and Sweden, it said.

The World Health Organization welcomed the report but said it does not recommend any changes to use of Pandemrix and that the vaccine remains on the list of recommended vaccines.

The European Medicines Agency also said that it would not change its assessment of the benefit-risk relating to use of the vaccine.

The Finnish institute said the association between narcolepsy and the Pandemrix vaccine needs more investigation with special attention on "infections and other stimuli in close time association with the pandemic vaccination."

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Key Data
DrugPandemrixCompany / LicenseeGlaxoSmithKlineTherapy ClassAnti-viral agentsProduct DescriptionPandemic (H1N1) AS03 adjuvanted vaccineCurrent IndicationSwine flu (H1N1)Market SectorAnti-infectivesDevelopment StatusApproved by the European CommissionFull specifications
--------------------------------------------------------------------------------

Pandemrix is an adjuvanted vaccine used in the prevention of the H1N1 (swine flu) virus infection and has been developed by GlaxoSmithKline Biologicals (GSK). The vaccine is a combination of H1N1 virus antigens and the adjuvant system AS03. The drug works by enhancing the natural immunity of the body.


Pandemrix - Adjuvanted H1N1 Influenza Vaccine

Phase I clinical trials of Pandemrix were completed and the results were submitted to the Committee for Medicinal Products for Human Use (CHMP) on 14 September 2009. On 25 September 2009, the CHMP and US Food and Drug Administration issued a positive opinion and recommended the drug's approval to the European Commission. The European Commission granted marketing authorisation for Pandemrix to GSK on 30 September 2009.

Key Data

Key Data:DrugPandemrixCompany / LicenseeGlaxoSmithKlineTherapy ClassAnti-viral agentsProduct DescriptionPandemic (H1N1) AS03 adjuvanted vaccineCurrent IndicationSwine flu (H1N1)Market SectorAnti-infectivesDevelopment StatusApproved by the European Commission

Pandemrix is an adjuvanted vaccine used in the prevention of the H1N1 (swine flu) virus infection and has been developed by GlaxoSmithKline Biologicals (GSK). The vaccine is a combination of H1N1 virus antigens and the adjuvant system AS03. The drug works by enhancing the natural immunity of the body.

Phase I clinical trials of Pandemrix were completed and the results were submitted to the Committee for Medicinal Products for Human Use (CHMP) on 14 September 2009. On 25 September 2009, the CHMP and US Food and Drug Administration issued a positive opinion and recommended the drug's approval to the European Commission. The European Commission granted marketing authorisation for Pandemrix to GSK on 30 September 2009.

The World Health Organization (WHO) officially declared on 11 June 2009 that Pandemrix should be used only for the Influenza A (H1N1) flu pandemic.

On 15 May 2009, GSK received orders from the US, France and Finland for the supply of the vaccine and agreed to supply the UK Government with 60 million doses of vaccine, the French Government with 50 million doses of vaccine and Finland with 5.3 million doses of vaccine

The total number of doses of Pandemrix ordered reached 291 million by July 2009. Out of these, 195 million doses of the vaccine worth $250m have to be supplied to the US Government as per the contract signed by GSK. Later, nine other countries ordered a further 96 million doses of Pandemrix.

It was expected that the first doses would be supplied to governments from September onwards and shipments between late 2009 and early 2010.

On 14 September 2009, GSK released the results of its first clinical trial, stating the use of its vaccine. By September 2009, the results of clinical trials on more than 39,000 people demonstrated that AS03 is safe when used with the influenza vaccine.

The authorisation of Pandemrix was allowed under 'Exceptional Circumstances', as the authorisation had to be awarded based only on Phase I clinical trials.

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www.drugdevelopment-technology.com/projects/pandemrix/

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Vaccines get a booster shot

Rupali Mukherjee, TNN, Feb 17, 2011, 04.42am IST


Read more: Vaccines get a booster shot - The Times of India timesofindia.indiatimes.com/business/india-business/Vaccines-get-a-booster-shot/articleshow/7511914.cms#ixzz1F00GrkUc

MUMBAI: Vaccines are back in favour. After being junked by pharma biggies some years back, now almost every drug major is investing in vaccines by acquiring or building on fresh capacities (organic or inorganic route). The evidence lies in pharma biggie Pfizer acquiring Wyeth and domestic major Shantha Biotech being snapped up by Sanofi a couple of years ago.

Presumably, vaccines which were earlier thought as a low-margin, low-growth industry, have emerged as one of the most lucrative segments of the industry, and domestic companies like Serum, Cadila and Wockhardt are trying to corner a piece of the action.

The Rs 1,500-crore domestic vaccine market-which has recorded a growth of 15% in the last fiscal-will continue to grow 15-20% over the years. Some industry players feel the sector can even outpace the pharma sector soon. Experts feel that the demand for vaccines is on the upswing because of the emphasis by the government to vaccinate children under the immunization programme. Combination vaccines like DPT (diphtheria, pertussis, tetanus), Hepatitis B, Hepatitis A, MMR (measles, mumps and rubella) and new generation vaccines like human papilloma are driving growth.

Ganesh Nayak, executive director, Zydus Cadila, said: "Owing to increasing public and private healthcare spending, a very high birth rate and prevalence of both infectious and chronic diseases, the domestic demand for vaccines in India will continue to grow at double-digit rate. With the takeover of Etna Biotech, part of the famous Berna vaccine group in Europe, Zydus has got the necessary assets to become an important player in the vaccine field."

Of late, governments across the world are following the theory of prevention as healthcare costs are becoming very expensive, feels Sujay Shetty, pharma leader, PwC India. "The perceived value of vaccines has, therefore, gone up," he says. For example, a Gardasil shot given to girls above 12-13 years to safeguard against cervical cancer costs around $300, while oncology treatments are exorbitant and cost over $25,000 a year.

Among the biggies, Sanofi Pasteur-the world's largest vaccine company-is a separate entity of Sanofi-Aventis devoted entirely to the vaccine business. Pfizer acquired Wyeth mainly due to its vaccine capability, notably the blockbuster vaccine for pneumonia, Prevnar, which has contributed over a billion dollar revenues already to the world's largest drug maker.


In the domestic market too, companies are increasingly investing in vaccines or ramping up existing facilities. Nayak adds: "Future cooperation with other innovative vaccine, companies cannot be ruled out if this will help to be faster on the market with new innovative products. We have also set up a dedicated vaccine development center which is working on research and development of high quality, value-added innovative vaccines."

Another major player, Pune-based Serum Institute, India, expects growth to be around 10-15% this year, up from last year's level. Says the company's executive director Suresh Jadhav: "The vaccine industry has been growing at 10-15% in India. However, it is much more in the developed countries because of the introduction of newer vaccines such as pneumococcal conjugate vaccine, rotavirus vaccine and HPV vaccine, which are sold at very high prices that cost almost $80-150 per dose, and for some vaccines two to three doses are required. While here, the largest selling vaccine is the measles vaccine, and also for Serum Institute."

Worldwide, there is increased focus on research and development in vaccines, which has been spurred by initiatives like the Gates foundation. Last year, the foundation pledged a huge investment of $10 billion in vaccines alone.

Nayak adds: "It is generally accepted that future growth rates are bigger in the vaccine sector than in the pharma sector alone. The vaccine market will continue to grow at the double-digit growth rate and we predict this rate 18-20% at least. The growth rates could be even higher if the economy continues to grow and government has surplus funds to invest in mass vaccination schemes".


timesofindia.indiatimes.com/business/india-business/Vaccines-get-a-booster-shot/articleshow/7511914.cms