Abstract
A major challenge for research on influenza vaccines is the selection of an appropriate animal model that accurately reflects the disease and the protective immune response to influenza infection in humans. Vaccines for seasonal influenza have been available for decades and there is a wealth of data available on the immune response to these vaccines in humans, with well-established correlates of protection for inactivated influenza virus vaccines. Many of the seminal studies on vaccines for epidemic influenza have been conducted in human subjects. Studies in humans are performed less frequently now than they were in the past. Therefore, as the quest for improved influenza vaccines continues, it is important to consider the use of animal models for the evaluation of influenza vaccines, and a major challenge is the selection of an appropriate animal model that accurately reflects the disease and the protective immune response to influenza infection in humans. The emergence of highly pathogenic H5N1 avian influenza (AI) viruses and the threat of a pandemic caused by AI viruses of this or another subtype has resulted in a resurgence of interest in influenza vaccine research. The development of vaccines for pandemic influenza presents a unique set of obstacles, not the least of which is that the demonstration of efficacy in humans is not possible. As the correlates of protection from pandemic influenza are not known, we rely on extrapolation of the lessons from seasonal influenza vaccines and on data from the evaluation of pandemic influenza vaccines in animal models to guide our decisions on vaccines for use in humans. The features and contributions of commonly used animal models for influenza vaccine research are discussed. The recent emergence of the pandemic 2009 H1N1 influenza virus underscores the unpredictable nature of influenza viruses and the importance of pandemic preparedness.