The roles of influenza virus haemagglutinin and nucleoprotein in protection: analysis using vaccinia virus recombinants.

Vaccinia virus recombinants expressing haemagglutinin (HA) or nucleoprotein (NP) from influenza virus A/PR/8/34 were used to investigate protective immunity in mice, with two protocols. Protection was assessed by mortality and morbidity rates and by lung virus titres after infection intranasally with A/PR/8/34. In the first protocol, mice immunized with vaccinia-HA recombinant virus and infected intranasally with A/PR/8/34 were almost totally protected, but mice immunized with vaccinia-NP virus were very poorly protected. In the second protocol, the recombinant viruses were used to stimulate in vitro T cells that are specific for HA and NP; both populations of T cells, when transferred to A/PR/8/34-infected mice, afforded good protection. The results indicate that an immune response specific for just HA provided protection that was almost indistinguishable from that provided by whole A/PR/8/34. On the other hand, immunization with vaccinia-NP provided poor protective immunity, despite the fact that transferred NP-specific T cells were very effective and vaccinia-NP immunization has previously been shown to stimulate cytotoxic T cells. These results demonstrate that a single viral antigen, delivered by live vaccinia virus, can provide effective protection, but that immunization for cross-protection against heterologous influenza virus remains elusive.