The Roles of Influenza Virus Haemagglutinin and Nueleoprotein in Protection: Analysis Using Vaccinia Virus Recombinants

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Abstract
Vaccinia virus recombinants expressing haemagglutinin (HA) or nucleoprotein (NP) from influenza virus A/PR/8/4 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 recombinaant 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 almsot 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.