Influenza A subtype cross-protection after immunization of outbred mice with a purified chimeric NS1/HA2 influenza virus protein.

Abstract

Influenza A/PR/8/34-derived chimeric (D) protein (SK&F 106160) composed of the first 81 amino acids (aa) of NS1 fused to the conserved 157 C-terminal aa of HA2 (NS1 1-81-HA2 65-222) was previously shown to induce H-2d-restricted protective cytotoxic T-lymphocyte (CTL) immunity in inbred mice. However, D protein, like other small peptides, exhibited haplotype dependence and was not immunogenic in H-2b and H-2K mice. A potential use of this antigen in humans and the role of T cells in any protection were evaluated in outbred Swiss and inbred CBF6F1 (H-2d/b) mice. Mice immunized with D protein and challenged by small-particle aerosol with a lethal dose of influenza virus were significantly protected against mortality from influenza A/H1N1 and A/H2N2 (p < 0.05-< 0.0000001), but not from A/H3N2 and influenza B viruses when compared with control mice. D protein did not induce serum virus-neutralizing antibody but caused virus to be cleared faster in immunized mice. Protection was long-lasting. In vivo depletion of either Lyt2 (CD8+) or L3T4 (CD4+) T cells with monoclonal antibodies led to abrogation of in vitro-generated CTL activity in CF6F1 mice and significant reduction in the protective efficacy of D protein against virus challenge in both Swiss and CF6F1 mice. These results suggest that protection was mediated by CD8+ and/or CD4+ cells and not antibody. Thus D protein, via a conserved sequence on the HA2 polypeptide, has the potential to induce partially cross-reactive CTL that may protect against influenza virus disease in humans.

• Authors: I N Mbawuike, S B Dillion, S G Demuth, C S Jones, T R Cate, R B Couch
• Journal: Vaccine (Vaccine) Vol. 12 Issue 14 Pg. 1340-8 (Nov 1994) ISSN: 0264-410X [Print] Netherlands
• PMID: 7856302 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Aerosols
• D protein, influenza A (A-PR-8-34-derived recombinant protein)
• Influenza Vaccines
• Recombinant Proteins
• Vaccines, Synthetic
• Viral Proteins

Topics

• Aerosols
• Animals
• CD4-Positive T-Lymphocytes (immunology)
• CD8-Positive T-Lymphocytes (immunology)
• Cross Reactions (immunology)
• Cytotoxicity Tests, Immunologic
• Female
• Flow Cytometry
• Influenza A virus (immunology)
• Influenza Vaccines (immunology)
• Mice
• Mice, Inbred BALB C
• Mice, Inbred C57BL
• Neutralization Tests
• Orthomyxoviridae Infections (prevention & control)
• Recombinant Proteins
• Vaccines, Synthetic (immunology)
• Viral Proteins (immunology)
• Virus Replication (immunology)