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.
D000818:Animals; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D006389:Hemagglutinins, Viral / Q000235:genetics / Q000502:physiology*; D007116:Immunization, Passive; D009980:Influenza A virus / Q000276:immunology / Q000302:isolation & purification / Q000502:physiology*; D008168:Lung / Q000382:microbiology; D051379:Mice; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins / Q000502:physiology*; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000517:prevention & control*; D016601:RNA-Binding Proteins; D011994:Recombinant Proteins / Q000502:physiology; D013601:T-Lymphocytes / Q000276:immunology / Q000637:transplantation; D014616:Vaccinia virus / Q000276:immunology / Q000502:physiology*; D014758:Viral Core Proteins; D014764:Viral Proteins / Q000502:physiology*; D014765:Viral Vaccines / Q000494:pharmacology*
D019267:Hemagglutinin Glycoproteins, Influenza Virus; D006389:Hemagglutinins, Viral; C048842:NP protein, Influenza A virus; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins; D016601:RNA-Binding Proteins; D011994:Recombinant Proteins; D014758:Viral Core Proteins; D014764:Viral Proteins; D014765:Viral Vaccines