GAITHERSBURG, MD. — An inactivated H5N1 influenza virus vaccine that a federal advisory panel has recommended for approval would, if approved, become the first vaccine for avian influenza licensed in the United States.
At a meeting of the Food and Drug Administration's Vaccines and Related Biological Products Advisory Committee, the panel agreed that that there were sufficient data to support the safety and effectiveness of the investigational vaccine during an avian flu pandemic or in situations of potential high-risk exposure. The vaccine is based on an A/Vietnam strain of the H5N1 avian influenza virus.
The proposed indication for the vaccine, manufactured by Sanofi Pasteur, is for active immunization against influenza disease caused by the H5N1 A/Vietnam/1203/2004 influenza virus and for primary vaccination of healthy adults aged 18–64. Two 90-mcg doses of the vaccine would be administered intramuscularly, 28 days apart.
If approved, the vaccine would not be available commercially but would be part of the prepandemic vaccine stockpile in the United States.
This “is an important step in the development of a pandemic influenza vaccine,” said panel chair Dr. Ruth A. Karron, professor in the department of international health, Johns Hopkins School of Hygiene and Public Health, Baltimore.
Throughout the meeting, panelists and FDA officials referred to the vaccine as an “interim” or “stopgap” vaccine. Many other vaccines are being developed that are potentially better than this vaccine, said Dr. Norman Baylor, director of the FDA's office of vaccines research and review.
Panelist Robert Webster, Ph.D., chair of the department of virology and molecular biology at St. Jude Children's Research Hospital, Memphis, said it would not be clear how well the current vaccine works unless it were used in an actual pandemic. Nevertheless, if the H5N1 influenza virus does acquire human-to-human transmissibility, there will not be enough time to produce enough vaccine, so “we need this stockpile,” he said.
The vaccine is manufactured with the same process used for the seasonal influenza virus vaccine, which several panel members said provided reassurance about its safety.
The vaccine contains a much higher amount of antigen than the seasonal flu vaccine, however, which raised some concerns about the potential for adverse effects.
Safety and efficacy data came from a prospective, multicenter randomized double-blind phase I/II trial launched in 2004 and conducted by the National Institute of Allergy and Infectious Diseases. Investigators measured hemagglutinin inhibition (HAI) immunogenicity in 452 adults, aged 18–64, who received two injections of different vaccine doses 28 days apart.
The response rate—at least a fourfold increase in the HAI titer 28 days after the injection—among those who received the 90-mcg dose was 23% after the first dose and 45% after the second dose, with a waning of the response rate to about 18% 6 months after the second dose, said Dr. Andrea James of the FDA's division of vaccines and related product applications.
The immunogenicity in this study is less than that usually seen in studies of seasonal influenza vaccine, she pointed out.
Dose-related injection site reactions were the most common side effects, with 85% of those receiving 90-mcg doses having at least one such reaction. Systemic events were less frequent, with about 40% developing headache and 30% developing malaise with the 90-mcg dose, Dr. James said.
The vaccine is also being investigated in a study of 259 elderly adults and a study of 125 children aged 2–9. Once the FDA makes a decision about licensing of the vaccine for people ages 18–64, the company will initiate discussions about expanding the age range for approval, according to Sanofi Pasteur.