H7N9

[dothedd]

6:04 p.m. EST January 22, 2014


Four more cases of deadly bird flu were reported in China on Wednesday, bringing the season's total in that country to 221. Fifty-seven people have died.

The surge in cases has health officials worldwide watching closely as hundreds of millions of Chinese begin to travel for Chinese New Year.

The H7N9 strain of influenza jumped from birds to humans only last year. It is extremely dangerous, causing severe illness in more than three quarters of people infected and death in more than one quarter, according to Chinese researchers.

It is called bird flu because the virus originated in birds and so far is transmitted to humans only by live poultry. Cooked meat is no risk.

All of this year's cases have been in China.

The surge in cases comes as China gets ready for what is called Spring Festival in Chinese. Known as Chinese New Year in the West, it begins Jan 31. People customarily travel to spend the holiday with family.

China estimates that 3.6 billion trips will be taken during the two-week holiday -- and many of those traveling will be taking or buying live chickens and ducks as gifts.

Humans can be infected by being in close contact with "infected live poultry, mostly in live bird markets or when slaughtering birds at home," the United Nations Food and Agriculture Organization said in a warning issued Tuesday.

So far, no sustained human-to-human transmission has occurred, according to the World Health Organization.

"Nothing can be predicted with certainty, but on present evidence, none of these viruses shows a potential to spread widely or cause an explosive outbreak," Margaret Chen, director-general of the World Health Organization, said Tuesday in Geneva.

Flu viruses are notorious for quickly mutating into new forms, but so far genetic analysis by the FAO shows that the H7N9 virus has not changed significantly since its emergence last year.

"We are watching closely the increasing number of confirmed cases that are being reported from China during the past few weeks," said Joseph Breese, an influenza expert with the Centers for Disease Control and Prevention in Atlanta. "Fortunately, Chinese health officials have not reported changes in the epidemiology of the virus that would lead us to believe it can easily spread between humans."

The fear is that it could all too easily do so, said Mike Osterholm, director of the Centers of Excellence for Influenza Research and Surveillance at the University of Minnesota in St. Paul. "The clock is ticking but we just don't know what time it is."

Several things about H7N9 worry health officials. A major concern is that unlike other flu strains, it doesn't make infected birds sick, so farmers don't know their flocks are infected.

Humans are the proverbial canary in the coal mine in this outbreak. "The way we know that we have H7N9 in poultry is that humans start to get sick," Osterholm said.

When testing shows a flock is ill, farmers have been reluctant to cull their birds because the animals seem healthy.

The birds breathe out the virus. That's different from other flu strains, which are excreted in feces.

"We don't know yet if there's an infectious cloud that comes off the bird markets that can infect nearby humans," Osterholm said. There have been cases in which people who lived close to a live bird market but didn't go in still got infected, he said.

The concern is that with so many cases appearing in eastern and southern China, and hundreds of millions of people traveling long distances to get home for the holidays, the virus could find a way to mutate into something that can easily pass between humans.

"We're in a 'stay tuned' moment right now," Osterholm said. "If that happens, then bets are off. It's potential pandemic time."

[grits]

The flu is killing people big time this year. If you had the vaccine, you could still get a particular flu but survive. It is the ones who didn't get the vaccine that are dying.

[dothedd]

4 new cases of H7N9 bird flu reported
Source: Xinhua | February 3, 2014, Monday 
four more human cases of H7N9 bird flu — including one death — were reported in China yesterday.

They included two cases, one of whom died, in Guangdong Province and one in the Guangxi Zhuang Autonomous Region.

A fourth case was an 8-year-old girl who has been to a live poultry market in central China’s Hunan Province. She is in a stable condition.

A 63-year-old man died on Saturday in Shenzhen in Guangdong, while the other case of Guangdong is a 37-year-old man from Zhongshan who is in a critical condition, said the provincial health department yesterday.

Guangxi reported its first case this year yesterday, a 75-year-old man from Liuzhou. He is in a critical condition.

The man had been in contact with live poultry before he fell ill on January 27, the regional health department said. This is the second case in Guangxi since 2009.

China has reported more than 100 human H7N9 cases — including more than 20 deaths — this year, mostly in Guangdong and Zhejiang Province.

Strengthened prevention and control measures include the closure of live poultry markets in some cities.

On Saturday, six new cases and one death were reported.

Of the new cases, two were in Guangdong, two in Zhejiang, one in Fujian Province and one in Hunan. Guangdong’s two cases were two boys, aged five and six, who are in a stable condition.

An 82-year-old H7N9 patient died on Friday in Guangdong.

Last Friday, Shanghai halted live poultry trading for three months. The city has reported eight H7N9 infections and four deaths this year.

[dothedd]

Jan 22, 2014 20:20:48 GMT -5 grits said:

The flu is killing people big time this year. If you had the vaccine, you could still get a particular flu but survive. It is the ones who didn't get the vaccine that are dying.

Grits .... You might find your answer here: www.cdc.gov/flu/about/qa/vaccineeffect.htm

That is a good question, but I have little time to do research, so if you find it please post the results. 

[dothedd]

New England Journal of Medicine Publishes Positive Data From Clinical Trial of Novavax’ Vaccine Against H7N9 Avian Flu


• Data are industry’s first from clinical trial of vaccine against A(H7N9) strain of influenza
• 81% of 5ug adjuvanted vaccine recipients had protective HAI levels
• 97% of 5ug adjuvanted vaccine recipients had anti-neuraminidase antibody responses
• Protective levels achieved from vaccinations within 116 days of the announced outbreak of novel lethal H7N9 virus
• Dose-sparing formulation shows significant potential utility in the event of a pandemic
• Vaccine safety consistent with previously tested adjuvanted pandemic vaccines
Rockville, MD (November 13, 2013)–/GlobeNewswire, Inc./-Novavax, Inc. (NASDAQ: NVAX) today announced that positive clinical data for the company’s virus-like particle (VLP) vaccine candidate against A(H7N9) influenza were published online in the Correspondence section of The New England Journal of Medicine. The correspondence can be found at: www.nejm.org/doi/full/10.1056/NEJMc1313186 and will appear in the December 26, 2013 print edition.

The study, conducted in 284 adult male and female subjects, examined the safety and immunogenicity of two administrations of Novavax’ A(H7N9) VLP vaccine candidate on day 0 and day 21. Subjects were administered either placebo, 15 or 45 μg of vaccine alone, or 5 or 15μg of vaccine with either 30 or 60 ISCO® units of the saponin-based ISCOMATRIX® adjuvant, developed by CSL Limited in Australia. Serology was assessed at Days 0, 21 and 35 post-first immunization.

The Novavax A(H7N9) VLP vaccine candidate was generally well tolerated, and the safety was in line with the company’s previous findings with its influenza VLP antigens using ISCOMATRIX® adjuvant. Overall, as with other adjuvanted influenza vaccines, there was an increase in transient local and systemic reactions in the adjuvanted in contrast to the non-adjuvanted formulations, but there were no treatment-related SAEs in the active groups. The A(H7N9) VLP vaccine candidate induced hemagglutination-inhibition (HAI) antibody titers of ≥1:40 (seroprotection) and a four-fold HAI antibody rise (serconversion) against H7N9 in 81%
of subjects at the 5μg dose of A(H7N9) antigen with 60 ISCO® units of adjuvant, and 73% of subjects receiving 5μg dose of A(H7N9) antigen with either adjuvant dose level. The vaccine also elicited anti-neuraminidase (NA) antibodies against N9 in 92 to 97% of subjects receiving 5μg with either adjuvant dose level.

The A(H7N9) influenza strain has emerged recently as a potential pandemic concern. Less than ten (10) days after the Chinese Health authorities announced an outbreak of this novel avian influenza in humans (137 total confirmed cases, including 45 deaths, to date), Novavax obtained the genetic sequence of the strain and commenced production of a recombinant vaccine. Clinical trial material was manufactured and released in late June 2013 with the first doses injected in humans in early July 2013. Less than four months after the novel A(H7N9) virus had been identified and sequenced, Novavax’ H7N9 VLP vaccine, with the higher-dose of ISCOMATRIX® adjuvant, has achieved immune responses likely to be protective in 81% of recipient subjects with as little as 5μg of antigen.

“The production and testing of a vaccine for a novel, lethal influenza virus in such a short time period validates the agility of Novavax’ technology in addressing pandemic threats,” said Dr. Lou Fries, the company’s Vice President of Clinical and Medical Affairs. “The performance of our vaccine candidate is particularly important in light of the speed with which pandemic outbreaks can unfold. Often, an initial outbreak of a novel influenza virus is followed by a more severe and widespread outbreak at the onset of the next fall and winter respiratory virus season, as seen in 2009 with H1N1. Unfortunately, vaccine makers in 2009 were unable to produce vaccine in advance of the second wave and there was little impact of vaccine upon H1N1 disease in the first year. Past H7-based vaccine candidates have been poorly immunogenic and thus could not be advanced as viable vaccine candidates. This risk appears to have been overcome by our H7N9 adjuvanted VLP vaccine.”

Stanley C. Erck, President and Chief Executive Officer of Novavax, added, “As evidenced by our correspondence in The New England Journal of Medicine, this is a critical accomplishment for pandemic preparedness. Building on the positive clinical results with our H5N1 VLP vaccine candidate from last October, these recently gathered data from our A(H7N9) influenza vaccine give further confirmation that the Novavax vaccine platform deserves to play a key role in addressing evolving pandemic threats. We have used recombinant VLP technology to demonstrate that timely responses are possible, and we are proud to be the first company to produce a viable H7N9 vaccine. Furthermore, we are pleased that HHS-BARDA has recognized this achievement and asked us to focus our pandemic vaccine development under our HHS-BARDA contract on our H7N9 vaccine candidate.”

About H7N9 Avian Flu
Following recognition of the first human infections with avian-origin influenza A(H7N9) and their attendant severity in March 2013, public health officials from around the world called for immediate and preemptive development of surveillance, diagnostic and clinical intervention tools in the event that the A(H7N9) virus becomes transmissible among humans. According to Keiji Fukuda of the WHO, there is high concern over potential for A(H7N9) to gain sustainable person-to-person transmissibility. He noted that over a two-month period in China, as many H7N9 cases occurred as caused by H5N1 cases over 10 years. Additionally, molecular genetic changes occurred, suggesting adaptation of the virus to humans. After a quiescent period during
the summer months, four new cases of human A(H7N9) disease have been reported since October 7, prompting concerns and expectations over the virus reemerging in human populations in the coming winter season.

About Novavax
Novavax, Inc. (Nasdaq: NVAX) is a clinical-stage biopharmaceutical company creating novel vaccines and vaccine adjuvants to address a broad range of infectious diseases worldwide. Using innovative proprietary recombinant protein nanoparticle vaccine technology, the company produces vaccine candidates to efficiently and effectively respond to both known and newly emergent diseases. Novavax is involved in several international partnerships, including collaborations with Cadila Pharmaceuticals of India, LG Life Sciences of Korea, PATH and recently acquired Isconova AB, a leading vaccine adjuvant company located in Sweden. Together, Novavax’ network supports its global commercialization strategy to create real and lasting change in the biopharmaceutical and vaccinology fields. Additional information about Novavax is available on the company’s website, novavax.com.

About ISCOMATRIX® adjuvant
ISCOMATRIX® adjuvant is made from saponin, cholesterol and phospholipid which, under defined conditions, form cage-like structures typically 40-50nm in diameter. The optimized ISCOMATRIX® adjuvant is well defined, has minimal impurities and does not use any materials of animal origin. Additionally, improvements have been made to the manufacturing processes to ensure it can be reproduced on a large scale. ISCOMATRIX

[dothedd]

ONE OF THE BEST RESOURCES I HAVE SEEN ON H7N9

www.uq.edu.au/vdu/VDUInfluenza_H7N9.htm

[dothedd]

UN agency warns risk of bird flu crossing China's borders grows

7 Feb 2014
The proliferation of the H7N9 bird flu virus among poultry in live-bird markets in Guangxi has "significantly increased the risk" it will spread to neighbouring countries, a United Nations agency...

5:28AM
Guangxi boy confirmed with H7N9 virus after mother contracts bird flu
China reports three new H7N9 bird flu deaths, toll hits 25...

[dothedd]

www.cidrap.umn.edu/infectious-disease-topics/h7n9-avian-influenza

H7N9 cases grow by 7, along with China poultry industry outcry
CIDRAP News | Feb 06, 2014
Beijing and four provinces report more cases to bring the second-wave total to 181 as poultry-farming groups seek to suppress publicity about H7N9 cases to minimize financial losses to the industry.
FEB 05, 2014

H7N9 letup as Guangxi detections prompt warning
CIDRAP News | Feb 05, 2014
China reports nine new H7N9 cases, as detections near Vietnam prompt an alert.

[dothedd]

Ten new H7N9 cases push outbreak total past 300

 CIDRAP News | Feb 04, 2014

The cases are from five provinces, mostly in the south, and include three deaths.

www.cidrap.umn.edu/infectious-disease-topics/h7n9-avian-influenza

[dothedd]

A(H7N9) VLP Antigen Dose-Ranging Study With Matrix-M1™ Adjuvant

This study is currently recruiting participants.
Verified March 2014 by Novavax
Sponsor:
Novavax
Collaborator:
Department of Health and Human Services
Information provided by (Responsible Party):
Novavax

ClinicalTrials.gov Identifier:
NCT02078674
First received: March 3, 2014
Last updated: NA
Last verified: March 2014
History: No changes posted

Purpose
This is a randomized, observer-blinded, placebo-controlled trial in adults 18 to 64 years old. Randomization will be stratified by age (18 to 49 years and 50 to 64 years) and by prior influenza immunization within the past three months. Subjects 18 to 49 years of age will comprise ~67% of subjects in each treatment group, and the balance will comprise subjects 50 to 64 years.

Each subject will receive two identical IM doses of test article at a 21-day interval (Day 0 and Day 21), in alternate deltoids. For each subject, study follow-up will span approximately 385 days total, or approximately 13 months from the first dose.

Condition Intervention Phase
Influenza (Pandemic)
Biological: Monovalent Avian Influenza VLP (H7N9)
Biological: Matrix-M1™ adjuvant
Biological: Placebo
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: A Phase I/II Randomized, Observer-Blinded, Dose-Ranging Study to Evaluate the Immunogenicity and Safety of Monovalent A/Anhui/1/13 (H7N9) Virus-Like Particle (VLP) Avian Influenza Antigen (Recombinant) in Healthy Adults With and Without Matrix-M1™


Resource links provided by NLM:

MedlinePlus related topics: Bird Flu Flu
Drug Information available for: Influenza Vaccines
U.S. FDA Resources

Further study details as provided by Novavax:

Primary Outcome Measures:
Assessment of Safety [ Time Frame: Day 0 to Day 384 ] [ Designated as safety issue: Yes ]
Counts (and percentages) of subjects with solicited local and systemic AEs over the seven days post-injection and all adverse events, solicited and unsolicited, including adverse changes in clinical laboratory parameters, over 42 days post-first injection. In addition, MAEs, SAEs, and SNMCs will be collected for one year.

Immunogenicity as assessed by hemagglutination-inhibiting (HAI) antibody titers against the vaccine-homologous A/Anhui/1/13 (H7N9) virus. [ Time Frame: Day 0 to Day 384 ] [ Designated as safety issue: No ]
Geometric mean titer (GMT) Geometric mean ratio (GMR) Seroconversion rate (SCR) Seroresponse rate (SRR)


Secondary Outcome Measures:
Immunogenicity as assessed by neuraminidase-inhibiting antibodies to N9. [ Time Frame: Day 0 to Day 384 ] [ Designated as safety issue: No ]

Estimated Enrollment: 610
Study Start Date: March 2014
Estimated Study Completion Date: July 2015
Estimated Primary Completion Date: July 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Group A
Placebo
Biological: Placebo
Experimental: Group B
High dose Monovalent Avian Influenza VLP (H7N9); IM; Day 0 and Day 21
Biological: Monovalent Avian Influenza VLP (H7N9)
Experimental: Group C
High dose Monovalent Avian Influenza VLP (H7N9) with Low dose Matrix-M1™ adjuvant; IM; Day 0 and Day 21
Biological: Monovalent Avian Influenza VLP (H7N9) Biological: Matrix-M1™ adjuvant
Experimental: Group D
Intermediate dose Monovalent Avian Influenza VLP (H7N9) with Low dose Matrix-M1™ adjuvant; IM; Day 0 and Day 21
Biological: Monovalent Avian Influenza VLP (H7N9) Biological: Matrix-M1™ adjuvant
Experimental: Group E
Low dose Monovalent Avian Influenza VLP (H7N9) with Low dose Matrix-M1™ adjuvant; IM; Day 0 and Day 21
Biological: Monovalent Avian Influenza VLP (H7N9) Biological: Matrix-M1™ adjuvant
Experimental: Group F
High dose Monovalent Avian Influenza VLP (H7N9) with High dose Matrix-M1™ adjuvant; IM; Day 0 and Day 21
Biological: Monovalent Avian Influenza VLP (H7N9) Biological: Matrix-M1™ adjuvant
Experimental: Group G
Intermediate dose Monovalent Avian Influenza VLP (H7N9) with High dose Matrix-M1™ adjuvant; IM; Day 0 and Day 21
Biological: Monovalent Avian Influenza VLP (H7N9) Biological: Matrix-M1™ adjuvant
Experimental: Group H
Low dose Monovalent Avian Influenza VLP (H7N9) with High dose Matrix-M1™ adjuvant; IM; Day 0 and Day 21
Biological: Monovalent Avian Influenza VLP (H7N9) Biological: Matrix-M1™ adjuvant

Eligibility

Ages Eligible for Study: 18 Years to 64 Years
Genders Eligible for Study: Both
Accepts Healthy Volunteers: Yes
Criteria
Inclusion Criteria:

Healthy adult male or female, 18 to 64 years of age,
Willing and able to give informed consent prior to study enrollment,
Able to comply with study requirements, and
Women of child-bearing potential must have a negative urine pregnancy test prior to each vaccination, and will be advised through the Informed Consent process to avoid becoming pregnant over the duration of the study, and must assert that they will employ an effective form of birth control for the duration of the study. Acceptable forms of birth control are: credible history of continuous abstinence from heterosexual activity or prior surgical sterilization, hormonal contraceptives (oral, injectable, implant, patch, ring), barrier contraceptives (condom or diaphragm), and intrauterine device (IUD). Women with an adequately documented history of surgical sterility, or ≥50 years of age and without menses for ≥1 year are exempt from urine pregnancy testing.
Exclusion Criteria:

Subjects will be excluded if they meet any of the following criteria:

Any ongoing, symptomatic acute or chronic illness requiring medical or surgical care.
Asymptomatic conditions or findings (e.g., mild hypertension, dyslipidemia) that are not associated with evidence of end-organ damage are not exclusionary provided that they are being appropriately managed and are clinically stable (i.e., unlikely to result in symptomatic illness within the time-course of this study) in the opinion of the Investigator.
Acute or chronic illnesses or conditions which may be reasonably predicted to become symptomatic if treatment were withdrawn or interrupted are exclusionary, even if stable.
Note that illnesses or conditions may be exclusionary, even if otherwise stable and clinically minor, due to therapies used to treat them (see exclusion criteria 3, 5, 8, 9).
Any grade 1 or higher (as based on the Toxicity Grading Scale [TGS]) abnormality in ALT, AST, alkaline phosphatase, total bilirubin, blood urea nitrogen, or creatinine levels.
Any grade 2 or higher (as based on the TGS) vital sign or clinical laboratory abnormality not specified in criterion 2 above. Note that any abnormal vital sign may be repeated at the Investigator's discretion.
Participation in research involving investigational product (drug / biologic / device) within 45 days before planned date of first vaccination.
History of a serious reaction to prior influenza vaccination.
History of Guillain-Barré Syndrome (GBS) within 6 weeks following a previous influenza vaccine.
Received any vaccine in the 4 weeks preceding the study vaccination; or any A(H7N9) avian influenza vaccine at any time.
Any known or suspected immunosuppressive condition, acquired or congenital, as determined by history and/or physical examination.
Chronic administration (defined as more than 14 continuous days) of immunosuppressants or other immune-modifying drugs within 6 months prior to the administration of the study vaccine. An immunosuppressant dose of glucocorticoid will be defined as a systemic dose ≥10mg of prednisone per day or equivalent. The use of topical, inhaled, and nasal glucocorticoids will be permitted.
Administration of immunoglobulins and/or any blood products within the 3 months preceding the administration of the study vaccine or during the study.
Acute disease at the time of enrollment (defined as the presence of a moderate or severe illness with or without fever, or an oral temperature >38.0°C on the planned day of vaccine administration).
Known disturbance of coagulation.
Women who are pregnant or breastfeeding, or plan to become pregnant during the study.
Suspicion or recent history (within one year of planned vaccination) of alcohol or other substance abuse.
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT02078674

Contacts
Contact: D. Nigel Thomas, Ph.D. 240-268-2023 [e-mail]

Locations
United States, California
Diablo Clinical Research Recruiting
Walnut Creek, California, United States, 94598
Contact: Lana Norman 925-930-7267
Principal Investigator: Helen Stacey, MD
United States, Florida
Miami Research Associates Recruiting
Miami, Florida, United States, 33143
Contact: Terry Piedra 305-279-0015
Principal Investigator: Eric Sheldon, MD
United States, Idaho
Advanced Clinical Research Recruiting
Meridian, Idaho, United States, 83642
Contact: Jessica Walukones 208-377-8653
Principal Investigator: Mark Turner, MD
United States, New York
Regional Clinical Research, Inc. Recruiting
Endwell, New York, United States, 13760
Contact: Susan Owen, RN, BSN 607-754-4081
Principal Investigator: Suchet Patel, MD
United States, South Carolina
Coastal Carolina Research Recruiting
Mt. Pleasant, South Carolina, United States, 29464
Contact: Allison Kennedy 843-856-3784
Principal Investigator: Cynthia Strout, MD
Sponsors and Collaborators
Novavax
Department of Health and Human Services
Investigators
Study Director: D. Nigel Thomas, Ph. D. Novavax, Inc.
More Information

Additional Information:
Novavax, Inc This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party: Novavax
ClinicalTrials.gov Identifier: NCT02078674 History of Changes
Other Study ID Numbers: FLU-MI7A-201
Study First Received: March 3, 2014
Last Updated: March 3, 2014
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by Novavax:
H7N9

Additional relevant MeSH terms:
Influenza, Human
Orthomyxoviridae Infections
RNA Virus Infections
Virus Diseases
Respiratory Tract Infections
Respiratory Tract Diseases

ClinicalTrials.gov processed this record on March 04, 2014

[dothedd]

New England Journal of Medicine Publishes Positive Data From Clinical
Trial of Novavax’ Vaccine Against H7N9 Avian Flu

www.novavax.com/download/releases/H7N9%20PR%20-%20FINAL%20501%20pm%20release.pdf

[Aman A.K.A. Ahamburger]

....

International Effort Underway to Control Bird Flu in Cambodia

[dothedd]

Phase 1/2 Clinical Trial of Its H7N9 Avian Influenza VLP Vaccine Candidate With Matrix-M(TM)

GAITHERSBURG, Md., March 10, 2014 (GLOBE NEWSWIRE) -- Novavax, Inc. (NVAX), a clinical-stage biopharmaceutical company focused on the discovery, development and commercialization of recombinant nanoparticle vaccines and adjuvants, today reported its financial results for the fourth quarter and year ended December 31, 2013 and announced the initiation of a Phase 1/2 clinical trial of its H7N9 avian influenza VLP vaccine candidate with its proprietary Matrix-M adjuvant. The trial is enrolling 610 healthy subjects to evaluate the safety and immunogenicity of this vaccine and adjuvant.

Novavax Business Highlights

2013 Achievements:

Reported data from two RSV F-protein nanoparticle vaccine trials, one in 330 women of childbearing age and the other in 220 elderly subjects, demonstrating strong immunogenicity of the RSV vaccine candidate;
Demonstrated in the RSV elderly subject trial that the vaccine could be administered concurrently with a seasonal influenza vaccine to elicit potentially protective levels of antibodies to both vaccine targets;
Initiated our H7N9 avian influenza VLP vaccine candidate program in April and published the industry's first H7N9 vaccine human clinical trial data showing highly protective levels of antibodies following vaccination in the December 26th issue of the New England Journal of Medicine;
Acquired Novavax AB (previously Isconova AB) and its saponin-based adjuvant Matrix-M to support Novavax' vaccine programs; and
Completed a successful $100 million secondary stock offering.
2014 Recent Events:

Extended the contract for Advanced Development of Recombinant Influenza Products and Pandemic Preparedness with HHS BARDA; and
Initiated a U.S.-based Phase 1/2 clinical trial of H7N9 avian influenza VLP vaccine candidate with Matrix-M, enrolling 610 healthy adult subjects between 18 and 64 years old, under the Company's HHS BARDA contract.
2014 Anticipated Events:

Release of top-line data from the ongoing Phase 2 clinical trial of the RSV F protein nanoparticle vaccine candidate in women of childbearing age in the second quarter of 2014;
Release of top-line data from the recently initiated Phase 1/2 clinical trial of the H7N9 avian influenza VLP vaccine candidate with Matrix-M in the second half of 2014;
Initiate a Phase 2 clinical trial of our RSV F protein nanoparticle vaccine in pregnant women in the fourth quarter of 2014; and
Initiate a Phase 2 clinical trial of our quadrivalent VLP seasonal influenza vaccine in the fourth quarter of 2014.
"We made substantial progress in advancing our RSV and influenza vaccine development programs during 2013 and I believe 2014 holds the potential for even greater accomplishments across our entire pipeline," said Stan Erck, president and CEO of Novavax, Inc. "Our rapid response to the emergence of an avian H7N9 influenza strain continues to demonstrate the power and flexibility of our vaccine and adjuvant technologies. This year we plan to report top-line results from our ongoing RSV and influenza studies, initiate our first RSV clinical trial in pregnant women and report top-line results from the first study of our H7N9 avian influenza vaccine candidate with our Matrix-M adjuvant. These will be important milestones for these programs for which I anticipate continued success in 2014."

Financial Results for the Fourth Quarter and Year Ended December 31, 2013

In connection with its acquisition on July 31, 2013, Novavax AB's operations have been included in the company's consolidated results of operations and financial position as of the acquisition date. Novavax reported a net loss of $14.1 million, or $0.07 per share, for the fourth quarter of 2013, compared to a net loss of $8.0 million, or $0.06 per share, for the fourth quarter of 2012. For the full year 2013, the net loss was $52.0 million, or $0.31 per share, compared to a net loss of $28.5 million, or $0.22 per share, for 2012.

Novavax revenue in the fourth quarter of 2013 increased 92% to $8.7 million as compared to $4.6 million for the same period in 2012. The increase in revenue was primarily due to the HHS BARDA amendment relating to H7N9 manufacturing and other activities and the PATH amendment to support the company's Phase 2 clinical trial in women of childbearing age.

Research and development expenses increased 69% to $16.3 million in the fourth quarter of 2013, compared to $9.6 million for the same period in 2012, primarily as a result of increased costs relating to the company's RSV and pandemic (H7N9) influenza clinical trials and higher employee-related costs. General and administrative expenses increased 65% to $4.1 million in the fourth quarter of 2013 as compared to $2.5 million for the same period in 2012, resulting primarily from Novavax AB's expenses and higher professional fees.

As of December 31, 2013, the company had $133.1 million in cash and cash equivalents and investments compared to $50.3 million as of December 31, 2012. Net cash used in operating activities for 2013 was $45.4 million compared to $18.2 million for 2012. The increase in cash usage from the prior year was primarily due to higher research and development spending, including the company's RSV and pandemic (H7N9) influenza clinical trials, as well as increased employee-related costs.

CONTINUED

[dothedd]

Conference Call

Novavax management will host its quarterly conference call today at 4:30 p.m. EDT. The dial-in number for the conference call is 1 [phone] (U.S. or Canada) or 1 [phone] (international). A webcast of the conference call can also be accessed via a link on the home page of the Novavax website (novavax.com) or through the "Investor Info"/"Events" tab on the Novavax website.

A replay of the conference call will be available starting at 7:30 p.m. on March 10, 2014 until midnight May 1, 2014. To access the replay by telephone, dial 1 [phone] (domestic) or 1 [phone] (international) and use passcode 2459615. The replay will also be available as a webcast and can be found on the "Investor Info"/"Events" on the Novavax website.

About Novavax

Novavax, Inc. (NVAX) is a clinical-stage biopharmaceutical company creating novel vaccines and vaccine adjuvants to address a broad range of infectious diseases worldwide. Using innovative proprietary recombinant protein nanoparticle vaccine technology, the company produces vaccine candidates to efficiently and effectively respond to both known and newly emergent diseases. Novavax is involved in several international partnerships, including collaborations with Cadila Pharmaceuticals of India, LG Life Sciences of Korea and PATH, and recently acquired Isconova AB, a leading vaccine adjuvant company located in Sweden. Together, Novavax' network supports its global commercialization strategy to create real and lasting change in the biopharmaceutical and vaccinology fields. Additional information about Novavax is available on the company's website, novavax.com.

[dothedd]

Mar 23, 2014 13:41:37 GMT -5 dothedd said:

New England Journal of Medicine Publishes Positive Data From Clinical
Trial of Novavax’ Vaccine Against H7N9 Avian Flu

www.novavax.com/download/releases/H7N9%20PR%20-%20FINAL%20501%20pm%20release.pdf

Thank you Aham for posting this article. 

[dothedd]

HKU team hail H7N9 flu vaccine 'breakthrough'
Research may lead to first single jab that protects against many flu viruses
PUBLISHED : Wednesday, 02 April, 2014, 3:35am
UPDATED : Wednesday, 02 April, 2014, 7:58am

NOTE:  PARAGRAPHS IN RED.... 

University of Hong Kong researchers have developed a vaccine that may be the first in the world to offer a shield against many influenza viruses - including the deadly H7N9 bird flu strain - in one simple shot.

The HKU team described it as a breakthrough for seasonal flu vaccines, which can usually only provide protection against one or a few specific viral subtypes each.

The study found the new vaccine helped 80 to 100 per cent of mice fight different strains of flu viruses.

"Current influenza vaccines target only specific and individual subtypes, but it is difficult for scientists to predict which types of a virus will cause the next pandemic," the lead researcher, associate professor of public health Dr Leo Poon Lit-man, told the South China Morning Post.

"That is the reason why we should study whether there is another way to offer a broader spectrum of protection against different subtypes of viruses."

But it might take years before the vaccine is tested in human clinical trials, Poon said.

HKU led the study with technical help from the United States' National Cancer Institute. It published the findings in international scientific journal Proceedings of the National Academy of Sciences of the United States of America yesterday.

The researchers used the vaccinia virus - the key ingredient in the smallpox vaccine - as a vaccine carrier. The vaccinia virus is known to be able to induce robust protection in mice against the H5 type of influenza A viruses.

They tested hundreds of mice infected with various viral strains, including H3N2, H1N1, H7N7 and the most recent to surface among humans, H7N9.

Of the mice that were injected with the vaccine, 80 to 100 per cent were protected from subsequent viral attacks.

Among those that did not receive a jab, none survived.

"An influenza pandemic caused by a novel strain of influenza A virus that is virulent and highly transmissible among humans will be of great global concern," HKU said in a statement.

"This vaccine provides a promising strategy for universal protection against new and emerging influenza viruses."

The H7N9 strain of bird flu first infected humans in the mainland's Yangtze River Delta and adjoining Anhui province in February last year.

By February 28 this year, there had been 375 human cases, 115 of them fatal, according to the World Health Organisation.

The development of the HKU vaccine for commercialization is likely to be outpaced by a US study on an experimental H7N9 vaccine.

That prospective vaccine is tipped to be the first to protect humans against the deadly virus.

In November, the US vaccine underwent its first human test conducted by biopharmaceutical company Novavax, based in Maryland. The company said results were encouraging.

[dothedd]

H7N9 avian flu

The influenza A (H7N9) virus is one subgroup among the larger group of H7 viruses that normally circulate among birds. A number of human infections of the H7N9 virus have been reported in eastern China, mostly in the Yangtze River Delta region since late March 2013. Some of the patients have died of severe pneumonia brought on by the virus.

Germ warfare: Hong Kong’s never-ending fight against viruses:
www.scmp.com/sites/default/files/styles/403x250/public/2013/11/29/afp_18jun13_fe_flu_490_mers_virus_saudi_outbreak_ny345_copy.jpg?itok=aucxYVUC

Since the fatal outbreak of Sars in 2003, Hong Kong has been battling to keep a succession of diseases at bay. Sarah Lazarus examines the readiness of the city’s defences against ever-evolving...

The influenza A (H7N9) virus is one subgroup among the larger group of H7 viruses that normally circulate among birds. A number of human infections of the H7N9 virus have been reported in eastern China, mostly in the Yangtze River Delta region since late March 2013. Some of the patients have died of severe pneumonia brought on by the virus.

Quarantine workers sterilise the Nam Yue wholesale market in Macau last week after traces of H7N9 were found. 
Mainland authorities have discovered H7N9 on a Guangdong poultry farm, just two weeks after the agriculture minister noted that the country's farms had so far been free from the deadly bird flu strain.

Xinhua reported last night that Guangdong provincial agriculture authorities had confirmed finding traces of H7N9 in chicken samples collected from the Zhuhai Jinfeng Poultry farm in Zhuhai - a facility that supplies poultry to Macau.

The disclosure comes two weeks after Agriculture Minister Han Changfu said on the sidelines of the National People's Congress in Beijing that the outbreak appeared contained to wet markets.

"First, the whole nation has so far not found a single case of poultry infected with H7N9," Han said at a March 6 press conference. "Secondly, no poultry farm has so far been found to have any trace of the virus."

Han said the virus should not deter people from eating chicken and noted that thorough cooking would kill the strain.

Traces of H7N9 in chickens from the Zhuhai farm were first discovered by Macau authorities last week, according to the Macau Daily News. Local authorities culled 7,500 birds in the Nam Yue wholesale market, including those supplied by the farm.

Macau later announced a 21-day ban on live poultry imports from the mainland, the Business Daily of Macau reported.

Xinhua said that samples taken from the Doumen district farm by the provincial centre for animal disease control tested positive for H7N9 on Friday. The results were confirmed by the Ministry of Agriculture's national laboratory on Tuesday.

Experts from the Guangdong provincial agriculture department have overseen the culling of more than 80,000 live chickens since last week. They also provided five tonnes of disinfectant.

The mainland has reported more than 120 human H7N9 cases this year, 36 resulting in deaths, according to Xinhua.

Gong Guifen, secretary general of China Poultry Industry Association, told Xinhua that finding the H7N9 virus on a poultry farm may severely impact the industry. The industry has suffered losses worth more than 40 billion yuan (HK$50.5 billion) since the first outbreak last March.

The Yangcheng Evening News reported yesterday that Guangdong agriculture authorities had issued an urgent notice to local authorities to step up H7N9 surveillance on farms and markets.

[dothedd]

Vaccine Against Bird Flu Readied, Just in Case
U.S. officials want to be prepared, but some doubt H7N9 will become pandemic

April 30, 2014
Posted: 2:00 PM


WEDNESDAY, April 30, 2014 (HealthDay News) -- A vaccine to protect people against a potential outbreak of H7N9 bird flu has shown promising results, according to a new report.

This flu, first seen in humans in China last year, is common among birds and chickens, but so far isn't known to spread from person-to-person. However, people who have come into contact with infected birds have been sickened.

"An effective H7N9 vaccine is achievable," said researcher Dr. Niranjan Kanesa-thasan, from Novartis Vaccines in Cambridge, Mass.

If H7N9 flu were to become a pandemic, this preliminary work would make it simple to ramp up vaccine production and do larger trials, he said.

This flu most commonly infects older people. As of late April, the World Health Organization said 139 cases of H7N9 flu were reported in China. More than 20 percent of those patients have died.

Robin Robinson, deputy assistant secretary for preparedness and response in the U.S. Department of Health and Human Services, said this vaccine is only one step his agency is taking to prepare for a pandemic flu outbreak.

"The vaccine described in this study is one of more than 150 medical countermeasures -- drugs, vaccines, and diagnostics -- the Biomedical Advanced Research and Development Authority has in the development pipeline in our quest to protect health during emergencies," he said.

This study -- published online April 30 in Science Translational Medicine -- "is an important step in moving this candidate vaccine forward," Robinson added.

Because it's impossible to know when the next pandemic will occur or which virus will cause it, Robinson said preparedness is key.

"We are working with multiple manufacturers, including Novartis, to develop H7N9 vaccine candidates, evaluate the candidates in clinical trials for safety and effectiveness, and stockpile H7N9 vaccine so our nation can respond quickly if this deadly virus emerges in the United States or becomes a pandemic," Robinson said.

In order to get an immune-system response, Kanesa-thasan said, the vaccine has to include a component called an adjuvant, in this case one called MF59.

This particular adjuvant is used in Europe to boost the effectiveness of flu vaccine, but has not been approved for use in the United States. "The pathway to approval of adjuvanted vaccine is long and arduous, as it requires significant evidence of safety and effectiveness," Kanesa-thasan said.

In addition, for the vaccine to be effective, two doses are needed -- one to prime the body's immune system and another to cue the body to produce antibodies, he said.

To develop the vaccine, Kanesa-thasan and colleagues used what's called synthetic virus technology after the virus's genes were sequenced.

In a trial of about 400 people, the resulting vaccine was tested in human volunteers, who developed antibodies to the H7N9 virus. However, the researchers can't be sure the vaccine is effective because those vaccinated haven't been exposed to the actual virus.

Still, some of the antibody responses were very similar to the antibody responses seen in patients that survived the H7N9 flu, the study authors said.

Dr. Marc Siegel, an associate professor of medicine at NYU Langone Medical Center in New York City, thinks the odds of the H7N9 virus ever becoming a pandemic are slim.

"I don't think H7N9 is going to turn into a pandemic. There has been no history of a bird flu mutating to the point where it became a human pandemic," he said.

But Siegel believes that creating a vaccine is a good idea, although he doesn't think it needs to be produced or stockpiled.

More information

For more information on H7N9 flu, visit the World Health Organization.

[dothedd]

From 2003 it took H5N1 human cases nearly 6-years to reach the 430'ish mark; it's taken H7N9 about 61 weeks.


CONTINUED:

virologydownunder.blogspot.com.au/2014/05/h5n1-versus-h7n9.html

[dothedd]

VACCINE NEWS

FDA issues emergency use authorization for influenza A/H7N9 rapid test
Published on May 5, 2014

H7N9 Virus


Hong Kong reported a new case of influenza A/H7N9 last week and the CDC warned that the virus could make its way to the U.S.

Influenza A/H7N9, a new strain of the avian influenza first identified in China in 2013, kills one in three people infected. The virus moved across China in two successive waves, crossing the border into Hong Kong, Taiwan and Malaysia.

The privately held Arbor Vita Corporation announced this week that the FDA issued an emergency use authorization for its AVC A/H7N9 influenza rapid test for the presumptive detection of the virus in patients with signs and symptoms of respiratory infection in conjunction with epidemiological risk factors.

“The AVC A/H7N9 Influenza Rapid Test is a potent early surveillance tool,” Dr. Peter Lu, the CEO of Arbor Vita Corporation, said. “This test is suitable for early, point of care screening in strategic locations such as borders checks, airports, US company clinics in China, etc. Early detected infections are then confirmed by molecular tests, such as PCR in large reference laboratories.”

“We are proud and excited to receive FDA’s authorization under an EUA for the first rapid test able to diagnose patients suffering from this deadly respiratory infection.” Lu said. “We applaud the FDA’s efforts to authorize the test. This test may prove to be critical at containing a potential avian influenza pandemic.”

Arbor Vita was approached by the U.S. Navy in spring 2013 to develop a simple and accurate test to detect the virus after Arbor Vita demonstrated success in developing a similar test for influenza A/H5N1. The test was required to be simple enough for non-laboratory personnel to use in the field.

“We have confirmed that Arbor Vita’s test can detect human H7N9 viruses. The dual testing system – Influenza A virus and A/H7N9 virus – clearly has a great advantage.” Dr. Leo Poon, an associate professor at the Center of Influenza Research and School of Public Health at the University of Hong Kong, said.

vaccinenewsdaily.com/medical_countermeasures/330674-fda-issues-emergency-use-authorization-for-influenza-ah7n9-rapid-test/

[dothedd]

Lack of bird flu checks on frozen chicken imports from China 

Published on Sunday, 11 May 2014 21:00

Mandalay – The authorities have failed to check for bird flu contamination in frozen chicken imports from China despite the disease outbreak, according to news reports.

China exports about 6 to ten tons of frozen chicken per day to Mandalay.

Many voice concern about the possible spread of bird flu as China has reported the detection of H7N9 virus infection. They fear for safety because of the absence of food contamination checks at local markets.

“Frozen chicken and chicken eggs from China have long entered Myanmar illegally via border gates. As domestic chicken prices increase, more from China are entering our country. With a lot more frozen chicken coming to Mandalay, officials should do casual or regular checks at markets and cold storage factories,” said Dr Kyaw Htin from Chicken and Eggs Producers Association.

“With no inspection of markets so far, public consumers feel insecure about eating those chicken. Moreover, the poultry farms along the route where chicken are carried are vulnerable to the disease. We have now submitted the matter to the departments concerned.”

Earlier this month, the association reportedly submitted the matter to the regional government and departments concerned, calling for prompt inspection.

The frozen chicken from China are usually kept in cold storage facilities in Mandalay and then distributed to markets.

Myanmar used to face H5N1 virus that caused great losses to poultry farms. In some farms, poultry deaths recur every year. The chicken seemed to be infected with the same type of virus.
About 400 people in China have been infected with H7N9 virus and over 40 of them died so far.

PHOTO:

www.elevenmyanmar.com/images/stories/2014/May/Daily_May_11_KSM_China_bird_flu.jpg

[dothedd]

Novavax's Influenza Vaccine Study Shows Adjuvant Efficiency
Sept 24, 2014 - 6 minutes ago

Novavax, Inc. (NVAX) announced positive top-line data from a dose-ranging, randomized, observer-blinded, placebo-controlled phase I/II study on its H7N9 avian influenza virus-like particle (VLP) vaccine candidate, H7N9 VLP.

The study was conducted under Novavax’s contract with the Biomedical Advanced Research and Development Authority (:BARDA) of the U.S. Department of Health and Human Services (HHS) for the development of VLP vaccines for influenza with pandemic potential.

The study evaluated the safety and immunogenicity of H7N9 VLP plus adjuvant Matrix-M in 610 healthy participants. H7N9 VLP and Matrix-M were well tolerated among the patients.

The study showed that addition of Matrix-M led to a clear immunogenicity benefit compared to unadjuvanted H7N9 VLP, thereby showing the effect of Matrix-M on antigen dose-sparing regimens. Participants receiving 3.75μg of H7N9 VLP in combination with Matrix-M showed statistically significantly greater immune responses than those receiving 15μg of H7N9 VLP without Matrix-M.

Additionally, participants receiving H7N9 VLP plus Matrix-M showed strong neuraminidase inhibiting antibody response.

This was the first study evaluating H7N9 VLP in combination with Matrix-M for influenza with pandemic potential.

We remind investors that in Feb 2011, Novavax was awarded a contract with BARDA worth up to $179 million for the advanced development and manufacturing of recombinant influenza vaccines for pandemic preparedness. In Sep 2014, Novavax modified the contract to exercise an option period, which extended the contract until Sep 2016.

Milestones to be achieved during the option period include development of the H7N9/Matrix-M adjuvant pandemic influenza vaccine and completion of a phase II study (expected to be initiated in 4Q14) on a quadrivalent seasonal influenza vaccine candidate.

[Aman A.K.A. Ahamburger]

Crazy stuff barb!


Newly-detected bird flu in Southeast Asia poses threat to animal health, people’s livelihoods

[dothedd]

H7N9: The Next Influenza Pandemic?
By Alex B. Berezow - November 3, 2014

Since May of this year, 440 Chinese people have been infected with a new strain of influenza subtype H7N9, and 122 of them have died. Though the case-fatality rate suggested by this data is greatly inflated by asymptomatic and mild (and hence, unreported) cases, a new analysis in Trends in Microbiology suggests that the virus has the potential to become the next influenza pandemic.

Where did this new H7N9 strain come from? Genetic analyses suggest that four different avian influenza viruses swapped genes in a process known as "reassortment." (See figure.)

www.realclearscience.com/journal_club/2014/11/03/h7n9_the_next_influenza_pandemic_108924.html

The influenza genome consists of eleven genes on eight RNA segments, meaning that each RNA segment encodes only one or two genes. (Pause just a moment to think about that: A microscopic particle consisting of a mere eleven genes is able to kill 250,000 to 500,000 human beings every single year. Incidentally,Ebola virus only has seven genes.)

Due to its genomic structure and the fact that a single animal can be infected by more than one strain at a time, influenza is prone to reassorting its genome. In other words, RNA segment #1 from influenza virus X can be replaced by the same RNA segment from influenza virus Y. In the case of H7N9, it is believed that the "H7" gene came from avian influenza subtype H7N3, recently found in Chinese ducks, and that the "N9" gene came from either avian influenza subtype H2N9 or H11N9, both of which have been found in migratory birds. The six remaining RNA segments appear to have come from two different strains of H9N2.

Such genetic shuffling is quite common and is often responsible for influenza pandemics. The reason is that new genetic combinations fool our immune systems; antibodies we might have against say, H1N1, are completely useless against H7N9 and other subtypes.

Currently, the H7N9 strain is infecting mostly elderly men with underlying health issues who likely came into direct contact with live poultry. But, this could change. Once the virus is in humans, natural selection may favor the production of viruses that transmit more easily between humans. Such a transition probably would require very slight mutations in the "H7" gene (more properly called HA), as well as the gene PB2, which encodes an enzyme that helps replicate the viral genome.

Disturbingly, the authors believe that H7N9 possesses a greater pandemic potential than H5N1, which already has been spreading around the globe. Indeed, the authors conclude:
"...these viruses exhibit high replicative ability and limited transmissibility in mammals, have acquired mammalian-adapting amino acid changes, may reassort with circulating human viruses (based on the reported coinfection of a patient with H7N9 and human H3N2 viruses), and readily acquire resistance to the NA inhibitor oseltamivir."

As always, there is no reason to panic, but you can be certain that epidemiologists are keeping a close eye on H7N9.

Source: Tokiko Watanabe, Shinji Watanabe, Eileen A. Maher, Gabriele Neumann, Yoshihiro Kawaoka. "Pandemic potential of avian influenza A (H7N9) viruses." 

[Deleted]

Probably it can not extinct humans. Some people will have natural immunity.

[Aman A.K.A. Ahamburger]

This is 5-8.. But Bird Flu Strain In China Spreads To Yorkshire Duck Farm. This was the one that was reported in Russia and South East Asia I do believe. It's also been found in Germany. For those keeping score, that's right across the entire northern half of the Eastern hemisphere with a MERS resurgence in the Mid East - and of course hemorrhagic fever spreading from west Africa... Stay

[dothedd]

A VERY INTERESTING READ!



Rick Bright, PhD 

Acting Director 

Influenza Division 

BARDA 

U.S. Department of Health and Human Services 

[e-mail]

.
• HHS/BARDA-supported H7N9 vaccines in clinical trials:
─ Novavax (recombinant-based VLP +/- Iscomatrix) (Matrix M)
─ Novartis (cell-based inactivated, subunit +/- MF59)
─ MedImmune (egg-based LAIV) – with NIH
─ GSK (egg-based inactivated, subunit +/- AS03)
• H7N1 vaccine study -initial dose finding studies
• H7N9 vaccine Phase 2 study
─ sanofi pasteur (egg-based inactivated, subunit) (Mix & Match Studies
conducted by NIH)
• In general, all vaccines well tolerated
• Limited preliminary data indicate that two doses of vaccine
delivered with adjuvant are needed to induce sufficient
immunity as measured by HAI or MN



United States Department of
Health & Human Services
Office of the Assistant Secretary for Preparedness and Response

www.who.int/phi/DAY2_19_Bright_PM_Dubai2014.pdf

[dothedd]

H7N9 showing signs of increasing adaption to humans
Novel H7N9 Hong Kong Ex-Shenzhen - H7 Human Adaptations

Recombinomics Commentary
December 30, 2014 23:00

The sequences from the first confirmed H7N9 case (68F) in Hong Kong in the 2014/2015 season, A/Hong Kong/8194273/2014, raised concerns due to evidence of human adaptation in four recently acquired internal genes. [[ The "internal genes" are the genes other than the two surface genes, H and N ]] The PB2 sequence is most closely related to avian H9N2 sequences, except it has the human adaptation E627K. In addition, two other internal genes (PB1 and NP) are closely related to the human H9N2 case (86M) in late 2013, A/Hong Kong/308/2014, while the PA sequence is closely related to the human H10N8 sequence, A/Jiangxi-Donghu/346/2013 (73F, also from late 2013).

However, the H7 sequence also has evidence for human adaption. Two changes, T160A and Q226L, were present in the initial cases in early 2013. However, cases from late 2013 and early 2014 were found in geographic or familial clusters, especially those in Guangdong Province. Although sequences from initial cases were made public, subsequent sequences were withheld, and most sequence data was from cases exported to Hong Kong, as was the case for the first case in the 2014/2015 season.

The H7 sequence belongs to a sub-clade that includes the three most recent sequences from the prior season (A/Hong Kong/8122430/2014, 85F collected 4/13; A/Hong Kong/5731/2014, 82F collected 4/8; A/Hong Kong/5581/2014, 65M collected 4/3) as well as A/Hong Kong/4495/2014, 0.5F collected 3/1; and A/Malaysia/228/2014, 67F collected 2/11).

This subclade has three non-synonymous changes that are almost exclusively limited to human cases. E113K is present in the six human H7 sequences above, as well as A/Hangzhou/17-1/2014 and A/chicken/Jiangxi/SD001/2013). L177I is in the six above, plus 2 more human sequences (A/Taiwan/1/2014 and A/Taiwan/2/2014), while N276D is in the six above, plus A/Huizhou/01/2013, A/Guangdong/1/2013, A/shanghai/05/2013, and A/Shanghai/1/2013. The presence of all three of these polymorphisms in the six member subclade, as well as addition isolates which are almost exclusively human, raises concerns that these three H7 polymorphisms represent further human adaptation.

The first Hong Kong case in 2014/2015 was from Shenzhen, where the first case (35F) in Guangdong province was just reported. No poultry link was cited for either case, and both have symptomatic contacts, raising concerns that the number and size of clusters this season will be markedly
---------------------------
This will keep considerable pressure on to get a vaccine stockpile, even if the number of cases isn't very high. If the number of cases is also high this "season" then the pressure for a vaccine will be considerably higher than it was before.

Because 1) it spreads so easily AND 2) because the incubation period is much shorter AND 3) because it can be spread before symptoms are apparent AND 4) because the early symptoms are the same as some other very common conditions, H7N9 is far more of a pandemic threat than Ebola, even despite that there are current partially efective treatments for H7N9 and none for Ebola and the H7N9 mortality rate is lower than Ebola, H7N9 is more of a danger than Ebola, IMHO.

[dothedd]

RE-POST OF IMPORTANCE....

www.who.int/phi/DAY2_19_Bright_PM_Dubai2014.pdf

[dothedd]

Genes make H7N9 nimble killer, study finds.....
Researchers are worried the bird flu strain could one day become a 'doomsday virus' capable of human-to-human infection


UPDATED : Friday, 09 January, 2015, 2:43am

Stephen Chen and Zhuang Pinghui

H7N9 could become "doomsday" virus. Stephen Chen and Zhuang Pinghui
A deadly bird-flu strain first reported among humans two years ago is a swift transformer loaded with more genetic ammunition than previously thought, a mainland study reveals.

Researchers found that much of the virus' deadly power came from within, and at least half of its six genes are capable of causing illness in humans.

They also found that H7N9 changed rapidly after finding a new host. In some cases mutations that helped it survive better in mammals appeared in just four days, enabling the virus to spread quickly and inflict more damage inside the new host.

The study, by a team at the Chinese Academy of Sciences' Key Laboratory of Pathogenic Microbiology and Immunology, was published in the Journal of Virology late last year.

Lead author Bi Yuhai said H7N9 was probably the most elusive avian flu virus that scientists had encountered.

Since its emergence early in 2013, several key questions remain unanswered, including why it causes so few symptoms in birds - making early detection extremely difficult - and why it is so lethally active in humans. So far, at least 175 of about 460 people known to have been infected with the virus have died.

"In just under two years H7N9 infected as many people as H5N1 did in more than a decade," Bi said. "H5N1 was deadly to birds. H7N9 has almost no effect on birds. That is quite puzzling.

"Scientists have deep concerns about H7N9. Some fear it could be one of the most likely candidates to evolve into a 'doomsday virus' capable of human-to-human infection."

The researchers' experiments on mice suggested that H7N9's deadliness to humans came not only from HA and NA - the two proteins on the surface of the virus that help it bind to and detach from host cells - but also three internal genes called PB2, NP and M.

The team, led by professors George #$%$ Gao and Frank Liu Wenjun, found that PB2 was likely the deadliest of the three. Repeated experiments showed that PB2 played a key role in causing a deadly immune reaction known as a cytokine storm in the mice.

Bi said the genes might lead to better treatments or a vaccine. "PB2 provides a clear, new target. Most vaccines and drugs today only target the two surface proteins, but our study confirmed that targeting PB2 inside could also be effective," he said. But just getting this far has not been easy. "We launched animal experiments soon after we received the viral strains in April last year. The situation was grim and we fought like soldiers in a battle," Bi said Cai Haodong, a specialist in infectious diseases with Beijing's Ditan Hospital, said the findings could play a role in prevention.

"I don't think they're significant for treatment but are meaningful for prevention," he said.


"In just under two years H7N9 infected as many people as H5N1 did in more than a decade," Bi said. "H5N1 was deadly to birds. H7N9 has almost no effect on birds. That is quite puzzling.

"Scientists have deep concerns about H7N9. Some fear it could be one of the most likely candidates to evolve into a 'doomsday virus' capable of human-to-human infection."

A deadly bird-flu strain first reported among humans two years ago is a swift transformer loaded with more genetic ammunition than previously thought, a mainland study reveals.  Researchers found that much of the virus' deadly power came from within, and at least half of its six genes are capable of causing illness in humans.

They also found that H7N9 changed rapidly after finding a new host. In some cases mutations that helped it survive better in mammals appeared in just four days, enabling the virus to spread quickly and inflict more damage inside the new host.

The study, by a team at the Chinese Academy of Sciences' Key Laboratory of Pathogenic Microbiology and Immunology, was published in the Journal of Virologylate last year.  Lead author Bi Yuhai said H7N9 was probably the most elusive avian flu virus that scientists had encountered.

Since its emergence early in 2013, several key questions remain unanswered, including why it causes so few symptoms in birds - making early detection extremely difficult - and why it is so lethally active in humans. So far, at least 175 of about 460 people known to have been infected with the virus have died.

"In just under two years H7N9 infected as many people as H5N1 did in more than a decade," Bi said. "H5N1 was deadly to birds. H7N9 has almost no effect on birds. That is quite puzzling.

"Scientists have deep concerns about H7N9. Some fear it could be one of the most likely candidates to evolve into a 'doomsday virus' capable of human-to-human infection."

The researchers' experiments on mice suggested that H7N9's deadliness to humans came not only from HA and NA - the two proteins on the surface of the virus that help it bind to and detach from host cells - but also three internal genes called PB2, NP and M.

The team, led by professors George Fu Gao and Frank Liu Wenjun, found that PB2 was likely the deadliest of the three. Repeated experiments showed that PB2 played a key role in causing a deadly immune reaction known as a cytokine storm in the mice.

Bi said the genes might lead to better treatments or a vaccine. "PB2 provides a clear, new target. Most vaccines and drugs today only target the two surface proteins, but our study confirmed that targeting PB2 inside could also be effective," he said. But just getting this far has not been easy. "We launched animal experiments soon after we received the viral strains in April last year. The situation was grim and we fought like soldiers in a battle," Bi said Cai Haodong, a specialist in infectious diseases with Beijing's Ditan Hospital, said the findings could play a role in prevention.

"I don't think they're significant for treatment but are meaningful for prevention," he said.  Li Lanjuan, who heads up an H7N9 team at the No1 Hospital Affiliated at Zhejiang University, said before the study was published that early treatment was vital. "We believe if a patient is treated with antiviral drugs at an early stage, the case rarely becomes severe. If they used a week later, the patient's condition is very likely to worsen," Li said .

In 2013, about a fifth of H7N9 patients treated by Li's team in Zhejiang died, well below the 39 per cent national average.

www.scmp.com/news/china/article/1677751/genes-make-h7n9-nimble-killer-study-finds