Prospects for Improved Immunization Against Influenza

  • Edwin D. Kilbourne

Abstract

Soon after the first isolation of influenza A virus from humans in 1933, effective artificial immunization against the disease was accomplished empirically with inactivated and attenuated viral vaccines. It is now known that immunity to influenza is mediated principally by antibodies to epitopes of the hemagglutinin (HA) and neuraminidase (NA) external glycoproteins of the influenza virion. Either antigen alone is effective, but only antibody to the HA is neutralizing and prevents infection. At its simplest, immunity to influenza can be achieved by parenteral injection of the HA or its components, or even by the administration of HA-specific antibody. Not inappropriately, therefore, the HA of influenza virus is the best studied of any viral protein. As a consequence, its three-dimensional structure has been determined, its antigenic sites have been localized with monoclonal antibody, and its biologic functions in cellular attachment and entry have been defined [1] (see Wilson, Chapter 2, this volume). Knowledge of its nucleotide-deduced amino acid sequence has encouraged the search for immunogenic oligopeptides of the HA protein, as well as their synthesis, with the expectation that such components can be used as highly specific vaccines. Alternatively and ideally, oligopeptides from conserved regions of the molecule might induce broad immunity to a wide range of virus variants.

Keywords

Toxicity Influenza Schiff Vaccinia Plague 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Wiley DC, Wilson IA, Skehel JJ (1981) Structural identification of the antibody binding sites of Hong Kong influenza hemagglutinin and their involvement in antigenic variation. Nature 289: 373–378PubMedCrossRefGoogle Scholar
  2. 2.
    Kilbourne ED (1975) Epidemiology of influenza. In Kilbourne ED (ed) The Influenza Viruses and Influenza. Academic Press, New York, p 483Google Scholar
  3. 3.
    Lamb RA, Zebedee SL, Richardson CD (1985) Influenza virus M2 protein is an integral membrane protein expressed on the infected-cell surface. Cell 40: 627–633PubMedCrossRefGoogle Scholar
  4. 4.
    Holland J, Spindler K, Horodyski F, Grabau E, Nichol S, VandePol S (1982) Rapid evolution of RNA genomes. Science 215: 1577–1585PubMedCrossRefGoogle Scholar
  5. 5.
    Scholtissek C, Rohde W, von Hoyningen V, Rott R (1978) On the origin of the human influenza virus subtype H2N2 and H3N2. Virology 87: 13–14PubMedCrossRefGoogle Scholar
  6. 6.
    Couch RB, Kasel JA, Six HR, Cate TR, Zahradnik JM (1984) Immunological reactions and resistance to infection with influenza virus. In Stuart-Harris C, Potter CW (eds) The Molecular Virology and Epidemiology of Influenza. Academic Press, New York p 119Google Scholar
  7. 7.
    Townsend ARM, Skehel J J (1984) The influenza A virus nucleoprotein gene controls the induction of both subtype specific and cross-reactive cytotoxic T cells. J Exp Med 160: 552–563PubMedCrossRefGoogle Scholar
  8. 8.
    Graves PN, Schulman JL, Young JF, Palese P (1983) Preparation of influenza virus sub viral particles lacking the HA1 subunit of hemagglutinin: Unmasking of cross-reactive HA2 determinants. Virology 126: 106–116PubMedCrossRefGoogle Scholar
  9. 9.
    Sitbon M, Gomard E, Hannoun C, Levy J-P (1983) Anti-influenza human T killer cells present an intertypic activity anti-A and -B type viruses in a secondary reaction in vitro. Clin Exp Immunol 54: 49–58PubMedCentralPubMedGoogle Scholar
  10. 10.
    Bennink JR, Yewdell JW, Gerhard W (1982) A viral polymerase involved in recognition of influenza virus-infected cells by a cytotoxic T-cell clone. Nature 296: 75–76PubMedCrossRefGoogle Scholar
  11. 11.
    Chanock RM, Murphy BR (1979) Genetic approaches to control of influenza. Perspect Biol Med 22: S37–S48PubMedGoogle Scholar
  12. 12.
    Schiff GM, Linnemann CC, Shea L, Lange B, Rottee T (1975) Evaluation of a live, attenuated recombinant influenza vaccine in high school children. Infect Immun 11: 754–757PubMedCentralPubMedGoogle Scholar
  13. 13.
    Bennink JR, Yewdell JW, Smith GL, Moller C, Moss B (1984) Recombinant vaccinia virus primes and stimulates influenza hemagglutinin-specific cytotoxic T cells. Nature 311: 578–579PubMedCrossRefGoogle Scholar
  14. 14.
    Webster RG, Askonas BA (1980) Cross-protection and cross-reactive cytotoxic T cells induced by influenza virus vaccines in mice. Eur J Immunol 10: 396–401PubMedCrossRefGoogle Scholar
  15. 15.
    Wilson IA, Niman HL, Houghten RA, Cherenson AR, Connolly ML, Lerner RA (1984) The structure of an antigenic determinant in a protein. Cell 37: 767–778PubMedCrossRefGoogle Scholar
  16. 16.
    Green N, Alexander H, Olson A, Alexander S, Shinnick TM, Sutcliffe JG, Lerner RA (1982) Immunogenic structure of the influenza virus hemagglutinin. Cell 28: 477–487PubMedCrossRefGoogle Scholar
  17. 17.
    Shapira M, Jibson M, Muller G, Arnon R (1984) Immunity and protection against influenza virus by synthetic peptide corresponding to antigenic sites of hemagglutinin. Proc Natl Acad Sei USA 81: 2461–2465CrossRefGoogle Scholar
  18. 18.
    Nestorowicz A, Tregear GW, Southwell CN, Martyn J, Murray JM, White DO, Jackson DC (1985) Antibodies elicited by influenza virus hemagglutinin fail to bind to synthetic peptides representing putative antigenic sites. Mol Immunol 22: 145–154PubMedCrossRefGoogle Scholar
  19. 19.
    Dreesman GR, Kennedy RC (1985) Anti-idiotypic antibodies: Implications of internal image-based vaccines for infectious diseases. J Infect Dis 151: 761–765PubMedCrossRefGoogle Scholar
  20. 20.
    Kilbourne ED (1984) Immunization strategy: Infection-permissive vaccines for the modulation of infection. In Chanock RM, Lerner RA (eds) Modern Approaches to Vaccines. Cold Spring Harbor Laboratory, New York, p 269Google Scholar

Copyright information

© Springer Science+Business Media New York 1986

Authors and Affiliations

  • Edwin D. Kilbourne

There are no affiliations available

Personalised recommendations