1887

Abstract

Equine infectious anemia virus (EIAV) infection of horses provides a valuable model for examining the natural immunological control of lentivirus infection and disease and the mechanisms of protective and enhancing vaccine immunity. We have previously hypothesized that the EIAV envelope (Env) proteins gp90 and gp45 are major determinants of vaccine efficacy, and that the development of protective immunity by attenuated viral vaccines may be associated with the progressive redirection of immune responses from immunodominant, variable Env segments to immunorecessive, conserved Env sequences. Whilst the antibody-neutralization determinants of Env have been defined, there are to date no comprehensive analyses of the lymphoproliferative (T-helper, Th) and cytotoxic T-cell (CTL) epitopes of the EIAV Env proteins. Thus, in the current study, synthetic-peptide methodologies were used to define regions of EIAV Env associated with protective vaccine immunity in a panel of 12 horses inoculated with the attenuated EIAV vaccine and two asymptomatic carrier horses infected experimentally with the virulent EIAV strain expressing the same Env protein as the vaccine strain. The results of these studies identified 17 broadly reactive Th peptides and six broadly reactive CTL peptides in the Env proteins of EIAV that were associated with protective immunity. Thus, these data provide for the first time a comprehensive mapping of EIAV Env-specific cellular regions that can be used to examine the development of protective immunity and to evaluate potential cellular immune determinants of protective immunity.

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2007-04-01
2024-03-29
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References

  1. Albright-Fraser D. G., Reid R., Graber V., Bailey E. 1996; Polymorphism of DRA among equids. Immunogenetics 43:315–317
    [Google Scholar]
  2. Bailey E. 1980; Identification and genetics of horse lymphocyte alloantigens. Immunogenetics 11:499–506
    [Google Scholar]
  3. Bailey E. 1983; Population studies on the ELA system in American standardbred and thoroughbred mares. Anim Blood Groups Biochem Genet 14:201–211
    [Google Scholar]
  4. Ball J. M., Rushlow K. E., Issel C. J., Montelaro R. C. 1992; Detailed mapping of the antigenicity of the surface unit glycoprotein of equine infectious anemia virus by using synthetic peptide strategies. J Virol 66:732–742
    [Google Scholar]
  5. Bogers W. M. J. M., Cheng-Mayer C., Montelaro R. C. 2000; Developments in preclinical AIDS vaccine efficacy models. AIDS 14, (Suppl.):S141–S152 [CrossRef]
    [Google Scholar]
  6. Chung C., Leib S. R., Fraser D. G., Ellis S. A., McGuire T. C. 2003; Novel classical MHC I alleles identified in horses by sequencing clones of reverse transcription-PCR products. Eur J Immunogenet 30:387–396 [CrossRef]
    [Google Scholar]
  7. Chung C., Mealey R. H., McGuire T. C. 2005; Evaluation of high functional avidity CTL to Gag epitope clusters in EIAV carrier horses. Virology 342:228–239 [CrossRef]
    [Google Scholar]
  8. Clements J. E., Montelaro R. C., Zink M. C., Amedee A. M., Miller S., Trichel A. M., Jagerski B., Hauer D., Martin L. N., Bohm R. P. 1995; Cross-protective immune responses induced in rhesus macaques by immunization with attenuated macrophage-tropic simian immunodeficiency virus. J Virol 69:2737–2744
    [Google Scholar]
  9. Cole K. S., Rowles J. L., Jagerski B. A., Murphey-Corb M., Unangst T., Clements J. E., Robinson J., Wyand M. S., Desrosiers R. C., Montelaro R. C. 1997; Evolution of envelope-specific antibody responses in monkeys experimentally infected or immunized with simian immunodeficiency virus and its association with the development of protective immunity. J Virol 71:5069–5079
    [Google Scholar]
  10. Cole K. S., Murphey-Corb M., Narayan O., Joag S. V., Shaw G. M., Montelaro R. C. 1998; Common themes of antibody maturation to simian immunodeficiency virus, simian-human immunodeficiency virus, and human immunodeficiency virus type 1 infections. J Virol 72:7852–7859
    [Google Scholar]
  11. Craigo J. K., Leroux C., Howe L., Steckbeck J. D., Cook S. J., Issel C. J., Montelaro R. C. 2002; Transient immune suppression of inapparent carriers infected with a principal neutralizing domain-deficient equine infectious anaemia virus induces neutralizing antibodies and lowers steady-state virus replication. J Gen Virol 83:1353–1359
    [Google Scholar]
  12. Craigo J. K., Li F., Steckbeck J. D., Durkin S., Howe L., Cook S. J., Issel C., Montelaro R. C. 2007; Discerning an effective balance between equine infectious anemia virus attenuation and vaccine efficacy. J Virol 79:2666–2677
    [Google Scholar]
  13. Craigo J. K., Durkin S., Sturgeon T. J., Tagmyer T., Cook S. J., Issel C. J., Montelaro R. C. 2007; Immune suppression of challenged vaccinates as a rigorous assessment of sterile protection by lentiviral vaccines. Vaccine 25:834–845 [CrossRef]
    [Google Scholar]
  14. Fraser D. G., Bailey E. 1998; Polymorphism and multiple loci for the horse DQA gene. Immunogenetics 47:487–490 [CrossRef]
    [Google Scholar]
  15. Fraser D. G., Oaks J. L., Brown W. C., McGuire T. C. 2002; Identification of broadly recognized, T helper 1 lymphocyte epitopes in an equine lentivirus. Immunology 105:295–305 [CrossRef]
    [Google Scholar]
  16. Fraser D. G., Leib S. R., Zhang B. S., Mealey R. H., Brown W. C., McGuire T. C. 2005; Lymphocyte proliferation responses induced to broadly reactive Th peptides did not protect against equine infectious anemia virus challenge. Clin Diagn Lab Immunol 12:983–993
    [Google Scholar]
  17. Hammond S. A., Cook S. J., Lichtenstein D. L., Issel C. J., Montelaro R. C. 1997; Maturation of the cellular and humoral immune responses to persistent infection in horses by equine infectious anemia virus is a complex and lengthy process. J Virol 71:3840–3852
    [Google Scholar]
  18. Hammond S. A., Issel C. J., Montelaro R. C. 1998; General method for the detection and in vitro expansion of equine cytolytic T lymphocytes. J Immunol Methods 213:73–85 [CrossRef]
    [Google Scholar]
  19. Hammond S. A., Raabe M. L., Issel C. J., Montelaro R. C. 1999; Evaluation of antibody parameters as potential correlates of protection or enhancement by experimental vaccines to equine infectious anemia virus. Virology 262:416–430 [CrossRef]
    [Google Scholar]
  20. Howe L., Leroux C., Issel C. J., Montelaro R. C. 2002; Equine infectious anemia virus envelope evolution in vivo during persistent infection progressively increases resistance to in vitro serum antibody neutralization as a dominant phenotype. J Virol 76:10588–10597 [CrossRef]
    [Google Scholar]
  21. Hussain K. A., Issel C. J., Schnorr K. L., Rwambo P. M., Montelaro R. C. 1987; Antigenic analysis of equine infectious anemia virus (EIAV) variants by using monoclonal antibodies: epitopes of glycoprotein gp90 of EIAV stimulate neutralizing antibodies. J Virol 61:2956–2961
    [Google Scholar]
  22. Issel C. J., Coggins L. 1979; Equine infectious anemia virus: current knowledge. J Am Vet Med Assoc 174:727–733
    [Google Scholar]
  23. Issel C. J., Horohov D. W., Lea D. F., Adams W. V., Hagius S. D., McManus J. M., Allison A. C., Montelaro R. C. 1992; Efficacy of inactivated whole-virus and subunit vaccines in preventing infection and disease caused by equine infectious anemia virus. J Virol 66:3398–3408
    [Google Scholar]
  24. Leroux C., Issel C. J., Montelaro R. C. 1997; Novel and dynamic evolution of equine infectious anemia virus genomic quasispecies associated with sequential disease cycles in an experimentally infected pony. J Virol 71:9627–9639
    [Google Scholar]
  25. Li F., Craigo J. K., Howe L., Steckbeck J. D., Cook S., Issel C., Montelaro R. C. 2003; A live attenuated equine infectious anemia virus proviral vaccine with a modified S2 gene provides protection from detectable infection by intravenous virulent virus challenge of experimentally inoculated horses. J Virol 77:7244–7253 [CrossRef]
    [Google Scholar]
  26. Lichtenstein D. L., Rushlow K. E., Cook R. F., Raabe M. L., Swardson C. J., Kociba G. J., Issel C. J., Montelaro R. C. 1995; Replication in vitro and in vivo of an equine infectious anemia virus mutant deficient in dUTPase activity. J Virol 69:2881–2888
    [Google Scholar]
  27. McGuire T. C., Crawford T. B., Henson J. B. 1971; Immunofluorescent localization of equine infectious anemia virus in tissue. Am J Pathol 62:283–294
    [Google Scholar]
  28. McGuire T. C., Tumas D. B., Byrne K. M., Hines M. T., Leib S. R., Brassfield A. L., O'Rourke K. I., Perryman L. E. 1994; Major histocompatibility complex-restricted CD8+ cytotoxic T lymphocytes from horses with equine infectious anemia virus recognize Env and Gag/PR proteins. J Virol 68:1459–1467
    [Google Scholar]
  29. McGuire T. C., Zhang W., Hines M. T., Henney P. J., Byrne K. M. 1997; Frequency of memory cytotoxic T lymphocytes to equine infectious anemia virus proteins in blood from carrier horses. Virology 238:85–93 [CrossRef]
    [Google Scholar]
  30. Mealey R. H., Zhang B., Leib S. R., Littke M. H., McGuire T. C. 2003; Epitope specificity is critical for high and moderate avidity cytotoxic T lymphocytes associated with control of viral load and clinical disease in horses with equine infectious anemia virus. Virology 313:537–552 [CrossRef]
    [Google Scholar]
  31. Mealey R. H., Sharif A., Ellis S. A., Littke M. H., Leib S. R., McGuire T. C. 2005; Early detection of dominant Env-specific and subdominant Gag-specific CD8+ lymphocytes in equine infectious anemia virus-infected horses using major histocompatibility complex class I/peptide tetrameric complexes. Virology 339:110–126 [CrossRef]
    [Google Scholar]
  32. Montelaro R. C., Ball J. M., Rushlow K. E. 1993; Equine retroviruses. In The Retroviridae pp 257–360 Edited by Levy J. A. New York: Plenum Press;
    [Google Scholar]
  33. O'Rourke K., Perryman L. E., McGuire T. C. 1988; Antiviral, anti-glycoprotein and neutralizing antibodies in foals with equine infectious anaemia virus. J Gen Virol 69:667–674 [CrossRef]
    [Google Scholar]
  34. Perryman L. E., O'Rourke K., McGuire T. C. 1988; Immune responses are required to terminate viremia in equine infectious anemia lentivirus infection. J Virol 62:3073–3076
    [Google Scholar]
  35. Raabe M. L., Issel C. J., Cook S. J., Cook R. F., Woodson B., Montelaro R. C. 1998; Immunization with a recombinant envelope protein (rgp90) of EIAV produces a spectrum of vaccine efficacy ranging from lack of clinical disease to severe enhancement. Virology 245:151–162 [CrossRef]
    [Google Scholar]
  36. Ridgely S. L., Zhang B., McGuire T. C. 2003; Response of ELA-A1 horses immunized with lipopeptide containing an equine infectious anemia virus ELA-A1-restricted CTL epitope to virus challenge. Vaccine 21:491–506 [CrossRef]
    [Google Scholar]
  37. Roederer M., Koup R. A. 2003; Optimized determination of T cell epitope responses. J Immunol Methods 274:221–228 [CrossRef]
    [Google Scholar]
  38. Rwambo P. M., Issel C. J., Hussain K. A., Montelaro R. C. 1990; In vitro isolation of a neutralization escape mutant of equine infectious anemia virus (EIAV). Arch Virol 111:275–280 [CrossRef]
    [Google Scholar]
  39. Sarkar S., Kalia V., Murphey-Corb M., Montelaro R. C. 2002; Detailed analysis of CD4+ Th responses to envelope and Gag proteins of simian immunodeficiency virus reveals an exclusion of broadly reactive Th epitopes from the glycosylated regions of envelope. J Immunol 168:4001–4011 [CrossRef]
    [Google Scholar]
  40. Wang S. Z. S., Rushlow K. E., Issel C. J., Cook R. F., Cook S. J., Raabe M. L., Chong Y. H., Costa L., Montelaro R. C. 1994; Enhancement of EIAV replication and disease by immunization with a baculovirus-expressed recombinant envelope surface glycoprotein. Virology 199:247–251 [CrossRef]
    [Google Scholar]
  41. Zhang W., Lonning S. M., McGuire T. C. 1998; Gag protein epitopes recognized by ELA-A-restricted cytotoxic T lymphocytes from horses with long-term equine infectious anemia virus infection. J Virol 72:9612–9620
    [Google Scholar]
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