Hopeful news on human H5N1 vaccine, but production concerns considerable

Aug 8, 2005 (CIDRAP News) – Positive results from a human vaccine against the H5N1 avian flu that is the prime candidate for causing the next influenza pandemic came out of the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH), this weekend. Still, the challenges to producing such a vaccine in the quantities needed in an actual pandemic lend a dose of reality to the news.

Trials of the vaccine on human volunteers began several months ago at three university-based centers in the United States—the University of Rochester, the University of Maryland at Baltimore, and the University of California, Los Angeles. The vaccine so far has been given to 452 healthy adults to ascertain the immune response and to evaluate its safety profile.

Early trials results, reported by the New York Times and the Washington Post Saturday, showed good results after an initial dose and a booster dose given 4 weeks later. NIAID Director Anthony Fauci is quoted in the Times story as saying, "It's good news. We have a vaccine."

Preliminary results obtained from 115 (some sources say 113) of the vaccine recipients showed a strong enough immune response to ward off the virus. Results are awaited on the remaining subjects, but Fauci said he expects them to parallel those already in. The doses that were most effective contained 90 micrograms of H5N1 antigen in each of two shots, compared with the 15 micrograms of antigen given via a single injection in typical annual flu vaccinations.

The vaccine, made by Sanofi Pasteur, will next be tested in adults over age 65, likely beginning in about a month, according to the Associated Press (AP), and trials in children will follow shortly thereafter. Safety issues will be examined in these groups as well as optimal dosing levels. Normally, older people, children, and people with chronic diseases are most at risk for complications of influenza. The H5N1 strain may not fit this pattern; mortality rates in the 1918 flu pandemic were highest in otherwise healthy young adults.

The high doses needed for protection against H5N1 pose obvious challenges in regard to production capacity. In a Wall Street Journal (WSJ)article today, Fauci said the 2 million US doses already ordered might cover only 450,000 people. Supplying even the amount of vaccine ordered for yearly US influenza vaccination programs is problematic, as evidenced by last flu season's shortage when the Chiron company was unable to produce the almost–50 million doses it was to supply to the United States. In a flu pandemic, vaccine for the worldwide population would be needed.

The new vaccine, like yearly flu vaccines, is grown in chicken eggs, so the amount that can be produced is dependent on the supply of eggs that producers can supply to vaccine companies. And the growth process takes several months. Experiments on cell-culture vaccines, which would circumvent these limitations, are under way, but their clinical use is far distant. Said Fauci in the Times article, "The critical issue now is, can we make enough vaccine, given the well-known inability of the vaccine industry to make enough vaccine?"

Infectious disease expert Michael Osterholm said the news is hopeful, but he expressed great concern over supply issues. Even though the dosage will likely be refined as study continues, he told CIDRAP News, "We're starting, from these results, with the amount of antigen needed to immunize a person standing at 12 times what's needed for a typical flu vaccination."

And the limiting factors aren't only the egg supply. "We need to quickly scale up capacity," said Osterholm, director of CIDRAP, which publishes this Web site. "Since the current annual vaccine-production capacity worldwide is about 1 billion doses of the 15 microgram–antigen vaccine, right now we have the ability to produce less than enough vaccine for 100 million people in the first year of a pandemic. This covers less than 2% of the 6.5-billion world population. The bottom line is that this will do little to stop or even arrest a worldwide pandemic."

The vaccine was made under a 2004 contract with NIH to develop and make 8,000 to 10,000 doses of a new vaccine based on the H5N1 avian flu strain circulating in Southeast Asia at that time. Vaccine testing has not been done on the strain as it now exists, pointed out Osterholm.

The federal government, through a separate contract in 2004, ordered 2 million more doses of the vaccine, to be made available to public health and laboratory workers in the event of an emergency and to encourage the manufacturer to ramp up the production process. Dr. Fauci told the AP over the weekend that the government is poised to order significantly more vaccine now that positive results are coming in.

Research into an effective human vaccine has been humming due to the fact that the H5N1 strain of avian flu that has caused massive poultry deaths in Asia has also caused at least 112 cases in humans, with almost 60 of them fatal. Experts agree that when the strain evolves to a point where efficient person-to-person transmission begins, a worldwide pandemic will quickly follow.

See also:

Mar 23, 2005, CIDRAP News story on the clinical trials

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