1887

Abstract

The level of heterosubtypic immunity (Het-I) and the immune mechanisms stimulated by a heterosubtypic influenza virus infection were investigated in pigs. Pigs are natural hosts for influenza virus and, like humans, they host both subtypes H1N1 and H3N2. Marked Het-I was observed when pigs were infected with H1N1 and subsequently challenged with H3N2. After challenge with H3N2, pigs infected earlier with H1N1 did not develop fever and showed reduced virus excretion compared with non-immune control pigs. In addition, virus transmission to unchallenged group-mates could be shown by virus isolation in the non-immune control group but not in the group infected previously with H1N1. Pigs infected previously with homologous H3N2 virus were protected completely. After challenge with H3N2, pigs infected previously with H1N1 showed a considerable increase in serum IgG titre to the conserved extracellular domain of M2 but not to the conserved nucleoprotein. These results suggest that antibodies against external conserved epitopes can have an important role in broad-spectrum immunity. After primary infection with both H1N1 and H3N2, a long-lived increase was observed in the percentage of CD8 T cells in the lungs and in the lymphoproliferation response in the blood. Upon challenge with H3N2, pigs infected previously with H1N1 again showed an increase in the percentage of CD8 T cells in the lungs, whereas pigs infected previously with H3N2 did not, suggesting that CD8 T cells also have a role in Het-I. To confer broad-spectrum immunity, future vaccines should induce antibodies and CD8 T cells against conserved antigens.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/0022-1317-82-11-2697
2001-11-01
2024-03-28
Loading full text...

Full text loading...

/deliver/fulltext/jgv/82/11/0822697a.html?itemId=/content/journal/jgv/10.1099/0022-1317-82-11-2697&mimeType=html&fmt=ahah

References

  1. Bikour M. H., Frost E. H., Deslandes S., Talbot B., Weber J. M., Elazhary Y. 1995; Recent H3N2 swine influenza virus with haemagglutinin and nucleoprotein genes similar to 1975 human strains. Journal of General Virology 76:697–703
    [Google Scholar]
  2. Black R. A., Rota P. A., Gorodkova N., Klenk H.-D., Kendal A. P. 1993; Antibody response to the M2 protein of influenza A virus expressed in insect cells. Journal of General Virology 74:143–146
    [Google Scholar]
  3. Brown I. H., Ludwig S., Olsen C. W., Hannoun C., Scholtissek C., Hinshaw V. S., Harris P. A., McCauley J. W., Strong I., Alexander D. J. 1997; Antigenic and genetic analyses of H1N1 influenza A viruses from European pigs. Journal of General Virology 78:553–562
    [Google Scholar]
  4. Brown I. H., Harris P. A., McCauley J. W., Alexander D. J. 1998; Multiple genetic reassortment of avian and human influenza A viruses in European pigs, resulting in the emergence of an H1N2 virus of novel genotype. Journal of General Virology 79:2947–2955
    [Google Scholar]
  5. Castrucci M. R., Donatelli I., Sidoli L., Barigazzi G., Kawaoka Y., Webster R. G. 1993; Genetic reassortment between avian and human influenza A viruses in Italian pigs. Virology 193:503–506
    [Google Scholar]
  6. Castrucci M. R., Campitelli L., Ruggieri A., Barigazzi G., Sidoli L., Daniels R., Oxford J. S., Donatelli I. 1994; Antigenic and sequence analysis of H3 influenza virus haemagglutinins from pigs in Italy. Journal of General Virology 75:371–379
    [Google Scholar]
  7. De Bruin T. G., Van Rooij E. M., De Visser Y. E., Bianchi A. T. 2000; Cytolytic function for pseudorabies virus-stimulated porcine CD4+ CD8dull+ lymphocytes. Viral Immunology 13:511–520
    [Google Scholar]
  8. de Jong J. C., van Nieuwstadt A. P., Kimman T. G., Loeffen W. L., Bestebroer T. M., Bijlsma K., Verweij C., Osterhaus A. D., Class E. C. 1999; Antigenic drift in swine influenza H3 haemagglutinins with implications for vaccination policy. Vaccine 17:1321–1328
    [Google Scholar]
  9. Doherty P. C., Christensen J. P. 2000; Accessing complexity: the dynamics of virus-specific T cell responses. Annual Review of Immunology 18:561–592
    [Google Scholar]
  10. Doherty P. C., Allan W., Boyle D. B., Coupar B. E., Andrew M. E. 1989; Recombinant vaccinia viruses and the development of immunization strategies using influenza virus. Journal of Infectious Diseases 159:1119–1122
    [Google Scholar]
  11. Epstein S. L., Lo C. Y., Misplon J. A., Lawson C. M., Hendrickson B. A., Max E. E., Subbarao K. 1997; Mechanisms of heterosubtypic immunity to lethal influenza A virus infection in fully immunocompetent, T cell-depleted, β2-microglobulin-deficient, and J chain-deficient mice. Journal of Immunology 158:1222–1230
    [Google Scholar]
  12. Epstein S. L., Stack A., Misplon J. A., Lo C. Y., Mostowski H., Bennink J., Subbarao K. 2000; Vaccination with DNA encoding internal proteins of influenza virus does not require CD8+ cytotoxic T lymphocytes: either CD4+ or CD8+ T cells can promote survival and recovery after challenge. International Immunology 12:91–101
    [Google Scholar]
  13. Flynn K. J., Belz G. T., Altman J. D., Ahmed R., Woodland D. L., Doherty P. C. 1998; Virus-specific CD8+ T cells in primary and secondary influenza pneumonia. Immunity 8:683–691
    [Google Scholar]
  14. Flynn K. J., Riberdy J. M., Christensen J. P., Altman J. D., Doherty P. C. 1999; In vivo proliferation of naïve and memory influenza-specific CD8+ T cells. Proceedings of the National Academy of Sciences, USA 96:8597–8602
    [Google Scholar]
  15. Haesebrouck F., Pensaert M. B. 1986; Effect of intratracheal challenge of fattening pigs previously immunised with an inactivated influenza H1N1 vaccine. Veterinary Microbiology 11:239–249
    [Google Scholar]
  16. Heinen P. P., van Nieuwstadt A. P., Pol J. M., de Boer-Luijtze E. A., van Oirschot J. T., Bianchi A. T. 2000; Systemic and mucosal isotype-specific antibody responses in pigs to experimental influenza virus infection. Viral Immunology 13:237–247
    [Google Scholar]
  17. Ito T., Couceiro J. N., Kelm S., Baum L. G., Krauss S., Castrucci M. R., Donatelli I., Kida H., Paulson J. C., Webster R. G., Kawaoka Y. 1998; Molecular basis for the generation in pigs of influenza A viruses with pandemic potential. Journal of Virology 72:7367–7373
    [Google Scholar]
  18. Kendal A. P., Pereira M. S., Skehel J. J. 1982 Concepts and Procedures for Laboratory-based Influenza Surveillance Washington, DC: US Department of Health and Human Services;
  19. Kimman T. G., De Bruin T. M., Voermans J. J., Peeters B. P., Bianchi A. T. 1995; Development and antigen specificity of the lymphoproliferation responses of pigs to pseudorabies virus: dichotomy between secondary B- and T-cell responses. Immunology 86:372–378
    [Google Scholar]
  20. Kurimura T., Hirano A. 1973; Cross immune reactions between A(H1N1) and A(H2N2) influenza viruses. Biken Journal 16:51–56
    [Google Scholar]
  21. Liang S., Mozdzanowska K., Palladino G., Gerhard W. 1994; Heterosubtypic immunity to influenza type A virus in mice. Effector mechanisms and their longevity. Journal of Immunology 152:1653–1661
    [Google Scholar]
  22. Loeffen W. L., Kamp E. M., Stockhofe-Zurwieden N., van Nieuwstadt A. P., Bongers J. H., Hunneman W. A., Elbers A. R., Baars J., Nell T., van Zijderveld F. G. 1999; Survey of infectious agents involved in acute respiratory disease in finishing pigs. Veterinary Record 145:123–129
    [Google Scholar]
  23. Mozdzanowska K., Furchner M., Maiese K., Gerhard W. 1997; CD4+ T cells are ineffective in clearing a pulmonary infection with influenza type A virus in the absence of B cells. Virology 239:217–225
    [Google Scholar]
  24. Mozdzanowska K., Maiese K., Furchner M., Gerhard W. 1999; Treatment of influenza virus-infected SCID mice with nonneutralizing antibodies specific for the transmembrane proteins matrix 2 and neuraminidase reduces the pulmonary virus titer but fails to clear the infection. Virology 254:138–146
    [Google Scholar]
  25. Mozdzanowska K., Maiese K., Gerhard W. 2000; Th cell-deficient mice control influenza virus infection more effectively than Th- and B cell-deficient mice: evidence for a Th-independent contribution by B cells to virus clearance. Journal of Immunology 164:2635–2643
    [Google Scholar]
  26. Neirynck S., Deroo T., Saelens X., Vanlandschoot P., Jou W. M., Fiers W. 1999; A universal influenza A vaccine based on the extracellular domain of the M2 protein. Nature Medicine 5:1157–1163
    [Google Scholar]
  27. Nguyen H. H., Moldoveanu Z., Novak M. J., van Ginkel F. W., Ban E., Kiyono H., McGhee J. R., Mestecky J. 1999; Heterosubtypic immunity to lethal influenza A virus infection is associated with virus-specific CD8+ cytotoxic T lymphocyte responses induced in mucosa-associated tissues. Virology 254:50–60
    [Google Scholar]
  28. Okuno Y., Matsumoto K., Isegawa Y., Ueda S. 1994; Protection against the mouse-adapted A/FM/1/47 strain of influenza A virus in mice by a monoclonal antibody with cross-neutralizing activity among H1 and H2 strains. Journal of Virology 68:517–520
    [Google Scholar]
  29. Riberdy J. M., Flynn K. J., Stech J., Webster R. G., Altman J. D., Doherty P. C. 1999; Protection against a lethal avian influenza A virus in a mammalian system. Journal of Virology 73:1453–1459
    [Google Scholar]
  30. Riberdy J. M., Christensen J. P., Branum K., Doherty P. C. 2000; Diminished primary and secondary influenza virus-specific CD8+ T-cell responses in CD4-depleted Ig−/− mice. Journal of Virology 74:9762–9765
    [Google Scholar]
  31. Russell S. M., Liew F. Y. 1979; T cells primed by influenza virion internal components can cooperate in the antibody response to haemagglutinin. Nature 280:147–148
    [Google Scholar]
  32. Samsom J. N., de Bruin T. G. M., Voermans J. J. M., Meulenberg J. J. M., Pol J. M. A., Bianchi A. T. J. 2000; Changes of leukocyte phenotype and function in the broncho-alveolar lavage fluid of pigs infected with porcine reproductive and respiratory syndrome virus: a role for CD8+ cells. Journal of General Virology 81:497–505
    [Google Scholar]
  33. Schulman J. L., Kilbourne E. D. 1965; Induction of partial specific heterotypic immunity in mice by a single infection with influenza A virus. Journal of Bacteriology 89:170–174
    [Google Scholar]
  34. Smirnov Y. A., Lipatov A. S., Gitelman A. K., Okuno Y., Van Beek R., Osterhaus A. D., Claas E. C. 1999; An epitope shared by the hemagglutinins of H1, H2, H5, and H6 subtypes of influenza A virus. Acta Virologica 43:237–244
    [Google Scholar]
  35. Sonoguchi T., Naito H., Hara M., Takeuchi Y., Fukumi H. 1985; Cross-subtype protection in humans during sequential, overlapping, and/or concurrent epidemics caused by H3N2 and H1N1 influenza viruses. Journal of Infectious Diseases 151:81–88
    [Google Scholar]
  36. Steinhoff M. C., Fries L. F., Karron R. A., Clements M. L., Murphy B. R. 1993; Effect of heterosubtypic immunity on infection with attenuated influenza A virus vaccines in young children. Journal of Clinical Microbiology 31:836–838
    [Google Scholar]
  37. Topham D. J., Doherty P. C. 1998; Clearance of an influenza A virus by CD4+ T cells is inefficient in the absence of B cells. Journal of Virology 72:882–885
    [Google Scholar]
  38. Treanor J. J., Tierney E. L., Zebedee S. L., Lamb R. A., Murphy B. R. 1990; Passively transferred monoclonal antibody to the M2 protein inhibits influenza A virus replication in mice. Journal of Virology 64:1375–1377
    [Google Scholar]
  39. Ulmer J. B., Fu T. M., Deck R. R., Friedman A., Guan L., DeWitt C., Liu X., Wang S., Liu M. A., Donnelly J. J., Caulfield M. J. 1998; Protective CD4+ and CD8+ T cells against influenza virus induced by vaccination with nucleoprotein DNA. Journal of Virology 72:5648–5653
    [Google Scholar]
  40. Van Leengoed L. A., Kamp E. M. 1989; A method for bronchoalveolar lavage in live pigs. Veterinary Quarterly 11:65–72
    [Google Scholar]
  41. Van Reeth K., Labarque G., Nauwynck H., Pensaert M. 1999; Differential production of proinflammatory cytokines in the pig lung during different respiratory virus infections: correlations with pathogenicity. Research in Veterinary Science 67:47–52
    [Google Scholar]
  42. Webster R. G., Askonas B. A. 1980; Cross-protection and cross-reactive cytotoxic T cells induced by influenza virus vaccines in mice. European Journal of Immunology 10:396–401
    [Google Scholar]
  43. Werner G. H. 1966; Heterotypic crossed immunity, in the mouse, between human influenza viruses of types A and A 2. Comptes Rendus Hebdomadaires des Seances de l’Academie des Sciences Serie D 263:1913–1916 (in French
    [Google Scholar]
  44. Wraith D. C., Askonas B. A. 1985; Induction of influenza A virus cross-reactive cytotoxic T cells by a nucleoprotein/haemagglutinin preparation. Journal of General Virology 66:1327–1331
    [Google Scholar]
  45. Yasukawa M., Inatsuki A., Kobayashi Y. 1988; Helper activity in antigen-specific antibody production mediated by CD4+ human cytotoxic T cell clones directed against herpes simplex virus. Journal of Immunology 140:3419–3425
    [Google Scholar]
  46. Zhou N. N., Senne D. A., Landgraf J. S., Swenson S. L., Erickson G., Rossow K., Liu L., Yoon K., Krauss S., Webster R. G. 1999; Genetic reassortment of avian, swine, and human influenza A viruses in American pigs. Journal of Virology 73:8851–8856
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/0022-1317-82-11-2697
Loading
/content/journal/jgv/10.1099/0022-1317-82-11-2697
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error