New vaccine approaches for seasonal and pandemic influenza.

Inactivated influenza vaccines have been available since the late 1940s for the prevention of influenza disease. Based on the available scientific evidence, many public health authorities, including the World Health Organization, recommend annual use of these vaccines for specific populations, including the elderly. Despite these recommendations, actual vaccination uptake rates are very limited in many countries. Influenza vaccine research is confounded by the variable nature of the influenza viruses and annual influenza epidemics and by non-specific clinical diagnostic criteria. These confounding factors complicate evaluation not only of overall vaccine effectiveness, but also of the relative efficacy and effectiveness of different vaccine formulations. This paper summarizes recent advances in the development of seasonal and (pre-)pandemic vaccines, discusses the methodologic constraints on influenza vaccine research, and proposes measures to reduce the level of potential bias and confounding in influenza vaccine research.