Protection against a lethal avian influenza A virus in a mammalian system

The question of how best to protect the human population against a potentia l influenza pandemic has been raised by the recent outbreak caused by an av ian H5N1 virus in Hong Kong, The likely strategy would be to vaccinate with a less virulent, laboratory-adapted H5N1 strain isolated previously from b irds. Little attention has been given, however, to dissecting the consequen ces of sequential exposure to serologically related influenza A viruses usi ng contemporary immunology techniques. Such experiments with the H5N1 virus es are limited by the potential risk to humans. An extremely virulent H3N8 avian influenza A virus has been used to infect both immunoglobulin-express ing (Ig(+/+)) and Ig(-/-) mice primed previously with a laboratory-adapted H3N2 virus. The cross-reactive antibody response was very protective, while the recall of CD8(+) T-cell memory in the Ig-/- mice provided some small m easure of resistance to a low-dose H3N8 challenge. The H3N8 virus also repl icated in the respiratory tracts of the H3N2-primed Ig(+/+) mice, generatin g secondary CD8+ and CD4(+) T-cell responses that may contribute to recover y. The results indicate that the various components of immune memory operat e together to provide optimal protection, and they support the idea that re lated viruses of nonhuman origin can be used as vaccines.