Vaccines against pandemic influenza: what can be done before the next pandemic?

We currently do not know which specific influenza subtype or isolate will cause the next influenza pandemic. However, 4 influenza virus hemagglutinin subtypes (H2, H5, H7, and H9) are considered the most likely candidates. Avian influenza viruses of the H5N1 subtype have received the most attention to this point, as their ability to spread within the human population remains the only barrier to emergence of a pandemic strain. Several vaccines have been tested against these potential pandemic viruses using standard methods for developing inactivated vaccines. In general, these vaccines have been poorly immunogenic, requiring high doses and multiple exposures to generate even modest antibody titers. The use of adjuvants to improve presentation of antigen and stimulate the immune system offers promise for enhanced immunity. Currently approved adjuvants, MF59 and Alum, can be readily incorporated into pandemic vaccines, while novel adjuvants are moving toward approval, but may still be years away from routine use. Thus, a prepandemic vaccine strategy that involves the stockpiling of both potential antigens and proven adjuvants may represent the best approach to deal with this looming threat.