Document 0485
 DOCN  M9550485
 TI    Influenza A subtype cross-protection after immunization of outbred mice
       with a purified chimeric NS1/HA2 influenza virus protein.
 DT    9505
 AU    Mbawuike IN; Dillion SB; Demuth SG; Jones CS; Cate TR; Couch RB;
       Department of Microbiology and Immunology, Baylor College of; Medicine,
       Houston, TX 77030-3498.
 SO    Vaccine. 1994 Nov;12(14):1340-8. Unique Identifier : AIDSLINE
       MED/95159654
 AB    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.
 DE    Aerosols  Animal  Cross Reactions/IMMUNOLOGY  Cytotoxicity Tests,
       Immunologic  CD4-Positive T-Lymphocytes/IMMUNOLOGY  CD8-Positive
       T-Lymphocytes/IMMUNOLOGY  Female  Flow Cytometry  Influenza
       Vaccine/*IMMUNOLOGY  Mice  Mice, Inbred BALB C  Mice, Inbred C57BL
       Neutralization Tests  Orthomyxoviridae Infections/PREVENTION & CONTROL
       Orthomyxoviruses Type A/*IMMUNOLOGY  Support, U.S. Gov't, P.H.S.
       Vaccines, Synthetic/*IMMUNOLOGY  Viral Proteins/*IMMUNOLOGY  Virus
       Replication/IMMUNOLOGY  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).