Chiron wins H5N1 vaccine contract; WHO says virus is changing

Oct 28, 2005 (CIDRAP News) – The US government has awarded Chiron Corp. a $62.5 million contract to make a vaccine for H5N1 avian influenza as part of efforts to prepare for a possible human flu pandemic.

Meanwhile, the World Health Organization (WHO) said today that recent isolates of the H5N1 virus from birds and humans in Asia show slight genetic changes from the isolate on which current experimental H5N1 vaccines are based. However, the WHO is not recommending changing the prototype strain used for vaccines at this point.

Chiron, based in Emeryville, Calif., said it would supply the vaccine to the government in 2006. It is not yet known how many people the vaccine would protect, because the dose size has yet to be determined in clinical trials, officials said.

The Department of Health and Human Services (HHS) has a stated goal of stockpiling enough H5N1 vaccine to vaccinate 20 million people. In September the agency awarded Sanofi Pasteur a $100 million contract to supply an H5N1 vaccine. The dose size for that vaccine also remains to be determined.

"An influenza vaccine effective against the H5N1 virus is our best hope of protecting the American people from a virus for which they have no immunity," HHS Secretary Mike Leavitt said in announcing the contract yesterday.

Chiron said it would make the vaccine at its plant in Liverpool, England, where the company's seasonal flu vaccine is made, but production of the H5N1 vaccine will not affect production of the seasonal vaccine.

Chiron won a contract from the National Institute of Allergy and Infectious Diseases (NIAID) in May 2004 to produce small amounts of an H5N1 vaccine for use in clinical trials. In yesterday's announcement, the company said it would provide the vaccine for NIAID studies "later this year."

The vaccine to be tested by NIAID and the one to be produced under the HHS contract are the same, Chiron spokeswoman Alison Marquiss told CIDRAP News. However, the vaccine for HHS will be in bulk form, whereas the vaccine for the NIAID will be in "filled and finished form." The NIAID will test various doses and formulations of the vaccine, she said.

Marquiss said plans call for making the HHS vaccine after production of this year's seasonal flu vaccine is finished, which should permit delivery of the experimental vaccine in the first half of 2006.

WHO cites changes in H5N1
The WHO said its monitoring of H5N1 viruses has revealed recent changes in the hemagglutinin (HA) genes of viruses from birds in several countries and from humans in Indonesia. HA is a surface protein on flu viruses that enables them to attach to and enter host cells; it also serves to identify the viruses to the human immune system. (In virus names like H5N1, "H5" signifies the hemagglutinin type.)

"Recent investigations have indicated that H5 haemagglutinins (HA) genes of viruses from birds in China, Indonesia, Japan, Mongolia, Russia, South Korea and Turkey, and 3 viruses from humans in Indonesia are genetically distinguishable from the prototype strains selected last year for influenza pandemic vaccine development," the WHO said. "There is also evidence of antigenic variation among the HA of recent viruses. However, their geographical spread and pathogenicity in human populations remain unclear."

The WHO said it does not recommend changing the H5N1 prototype strains chosen previously for vaccine development. But the agency said its "H5 Reference Laboratory Network" has begun developing H5N1 vaccine prototype strains from the recent viruses.

There is no guarantee that the experimental H5N1 vaccines now under development would work in the event of a pandemic, since the virus is likely to evolve further before that happens. But experts hope that the vaccines would be close enough to the pandemic strain to provide at least some cross-protection. The viral changes reported by the WHO seem to suggest that the vaccines now in development would be less likely to work well, though the WHO didn't say that.

The agency said it urgently needs analyses of more recent H5N1 viruses from both animals and humans "in order to obtain a better understanding of the evolution of the viruses and their antigenic relationships." The statement called on countries to quickly share viral isolates and specimens with the WHO lab network.

Progress on other avian flu vaccines
In other news, Chiron today announced promising preliminary results in a clinical trial of a vaccine for another avian flu virus that has been known to infect humans, known as H9N2. The virus caused serious illness in three people in Hong Kong in 1999 and 2003 and is viewed as capable of evolving into a pandemic strain.

Four different doses of Chiron's experimental H9N2 vaccine were tested in 96 people. Some of the doses contained an adjuvant (a substance that stimulates the immune system) called MF59. All the formulations containing MF59 generated antibody levels believed high enough to protect a person from the virus, the company said. The lowest dose used was 3.75 micrograms, only a quarter of the amount used in seasonal flu vaccines.

Vaccine formulations without MF59 generated significantly lower levels of antibodies, the company said. The trial was supported by the NIAID, which awarded Chiron a contract in August 2004 to make up to 40,000 doses.

Progress on still another avian flu vaccine was reported by the European Union (EU) Commission yesterday. Researchers from several countries have developed an experimental vaccine for the H7N1 virus, which is viewed as another potential pandemic strain, the EU statement said.

H7N1 caused deadly outbreaks in Italian poultry in 1999 and was related to the H7N7 virus, which devastated Dutch poultry flocks in 2003, the EU said. European researchers reported recently that antibodies to H7 viruses were found in Italian poultry workers in 2003.

The H7N1 vaccine was developed by the "FLUPAN" consortium, including flu experts from the United Kingdom, Italy, Norway, and Sanofi Pasteur in France, the EU statement said. They used reverse genetics to create the vaccine, called RD-3.

"The risk of H7 emerging as a pandemic influenza strain is considered to be lower than H5N1," the EU statement said. "Nonetheless, it is expected that the H7 FLUPAN research will be a valuable resource for pandemic vaccine development in the future."

See also:

Oct 27 HHS news release
http://archive.hhs.gov/news/press/2005pres/20051027.html

Oct 15 Journal of Infectious Diseases article on H7 viruses
http://www.journals.uchicago.edu/doi/full/10.1086/444390

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