June 30, 2008

The European Union has approved its first pre-pandemic vaccine, targeted against H5N1 influenza. The vaccine, manufactured by GlaxoSmithKline (GSK) and marketed under the name Prepandrix, uses a proprietary oil-and-water adjuvant to substantially reduce the amount of antigen needed to generate an immune response. The announcement coincided with the IDSA-sponsored Seasonal and Pandemic Influenza 2008 conference this May.

The GSK vaccine uses antigen derived from the same strain of virus, A/Vietnam/1194/04, as a vaccine developed earlier by Sanofi Pasteur and included in the U.S. stockpile. However, the GSK vaccine generated immune responses predictive of protection using just 3.8 μg of antigen, compared to 90 μg in the unadjuvanted Sanofi Pasteur vaccine currently in the U.S. stockpile. Seasonal influenza vaccines generally include 15 μg of antigen per virus strain.

The H5N1 vaccine strain is a clade 1 virus, but clade 2 has become dominant throughout Southeast Asia, according to data presented by Nancy J. Cox, PhD, of the Centers for Disease Control and Prevention (CDC) National Center for Immunization and Respiratory Diseases, in her presentation at the conference. However, the vaccines show some degree of cross-reactivity with other strains, Dr. Cox said.

IDSA National and Global Public Health Committee Chair Andrew T. Pavia, MD, FIDSA, of the University of Utah Medical Center, said the question now is, “Do we want to stockpile vaccines in warehouses, or in people’s arms?” In other words, in the absence of a pandemic, how widely should these vaccines be used?

If an H5N1 pandemic strikes, it would take months to produce a vaccine based on the pandemic strain, noted Jesse L. Goodman, MD, MPH, FIDSA, director of the Center for Biologics Evaluation and Research at the Food and Drug Administration, during his presentation. Those who received pre-pandemic vaccine ahead of time might have some immunity. The pre-pandemic vaccine might even serve as a priming vaccine, with the pandemic-strain vaccine acting as a booster.

However, the 1976 swine flu outbreak provides some cautionary lessons on mass vaccination in response to an uncertain threat. One lesson: “Expect the unexpected,” he said. Milder-than-expected influenza, a manufacturing mix-up, and, finally, Guillain-Barre syndrome scuttled the swine flu mass vaccination campaign. If H5N1 pre-pandemic vaccination is undertaken, surveillance would be essential to detect unusual events. Effective communications about benefits and risks also would be crucial.

Of course, there is no guarantee the next influenza pandemic will be caused by H5N1. But considerable progress has been made as a result of H5N1 that can be applied to any influenza pandemic, as well as to seasonal influenza. In his presentation, Robin Robinson, PhD, director of the newly created federal Biomedical Advanced Research Development Authority (BARDA), listed $1.3 billion in contracts awarded to companies to expand domestic vaccine manufacturing. The agency also is supporting research combining antigens and adjuvants from different manufacturers in order to minimize the amount of antigen needed, a novel approach called “mix-n-match.”

IDSA strongly supported the creation of BARDA, an agency intended to encourage development of biomedical tools against biological, chemical, nuclear, and radiological threats to national security. In addition to influenza vaccine development, the agency is funding development of antivirals and rapid diagnostics for influenza and other infectious diseases.

More from Seasonal and Pandemic Influenza 2008 is available online.

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