“We have been asked to provide up to 20 million doses of the vaccine, in addition to the 2 million we have already agreed to supply,” Len Lavenda, spokesman for Sanofi-Pasteur, Swiftwater, Pa., told FAMILY PRACTICE NEWS. The contract would be contingent on the vaccine being approved after thorough testing in clinical trials. Currently, only preliminary information is available about immunogenicity in adults, and trials in children and the elderly have yet to start.
If the vaccine is approved, the 22 million doses will be added to the Strategic National Stockpile of drugs, and distributed only in the event of an H5N1 pandemic.
Although the first clinical trial of 452 healthy adults aged 18–64 years is ongoing, early data show immune response in the 113 subjects for whom serology is available, John Treanor, M.D., said in an interview. The trial is testing four doses of the vaccine (7.5 mcg, 15 mcg, 45 mcg, and 90 mcg). Subjects received an initial vaccination plus a booster of the same dose given about a month later.
All doses produced some response, but only two 90-mcg doses gave a response robust enough to inspire confidence about immunity, said Dr. Treanor, principal investigator of the trial conducted at the University of Rochester (N.Y.).
With the 90-mcg doses, “We're confident the immune response would be protective against the H5 virus,” he said. “There was definitely a dose-response reaction.”
But the large dose required to produce optimal response could put a strain on manufacturing, making it tough for the government to meet its preliminary quota of 22 million doses, said Anthony Fauci, M.D., director of the National Institute of Allergy and Infectious Diseases.
“This will put an extra strain on the production issue—which has been an issue of concern even before this,” he told this newspaper. “We've been talking about the lack of ability to manufacture a global vaccine for a long time. This underscores the issue. It's a problem that will only be solved by getting more companies involved.”
Several factors affect vaccine production capacity, said Mr. Lavenda. The concentration of antigen in each dose is one factor.
However, he said, the company recently began construction of a new influenza vaccine facility, which will more than double its U.S. capacity. The facility will probably come online by 2008. An overhaul of the company's French facility, which will double its capacity, is in the works as well.
Researchers will be searching for ways to decrease the antigen load in each dose, Dr. Treanor said. “We'll be looking at reducing the dose but achieving the same response, maybe by adding adjuvants or going a different route of administration.”
The vaccine must also still be tested in children and the elderly, he noted. But the preliminary results in adults are raising hopes for similarly good responses in other age groups. The quick turnaround on the development of this vaccine also shows that vaccines against other emergent strains could be produced rapidly, Dr. Treanor said.
Work on the vaccine began in early 2004, when the initial viral sample was isolated in Southeast Asia. Proceeding from virus isolation to vaccine clinical trials in little more than 1 year is unprecedented, Dr. Treanor and Dr. Fauci said.
“The most important part of this study is that for the first time we have gone through the whole process of identifying the virus, making a genetically engineered seed virus, producing the vaccine, and then getting immune results 4 months from vaccination,” said Dr. Treanor.
Having such a process in place gives some assurance that researchers would be able to respond quickly to any antigenic drift the H5 virus might experience, Dr. Fauci said. “The virus might change so significantly that this vaccine would offer much less protection. This exercise that we have gone through is an important dry run in being able to produce a vaccine as quickly as possible.”
Michele G. Sullivan