Skip to main content
NCBI home page
Journal of Virology logoLink to Journal of Virology
. 1992 Jun;66(6):3398–3408. doi: 10.1128/jvi.66.6.3398-3408.1992

Efficacy of inactivated whole-virus and subunit vaccines in preventing infection and disease caused by equine infectious anemia virus.

C J Issel 1, D W Horohov 1, D F Lea 1, W V Adams Jr 1, S D Hagius 1, J M McManus 1, A C Allison 1, R C Montelaro 1
PMCID: PMC241120  PMID: 1316455

Abstract

We report here on a series of vaccine trials to evaluate the effectiveness of an inactivated equine infectious anemia virus (EIAV) whole-virus vaccine and of a subunit vaccine enriched in EIAV envelope glycoproteins. The inactivated vaccine protected 14 of 15 immunized ponies from infection after challenge with at least 10(5) 50% tissue culture-infective doses of the homologous prototype strain of EIAV. In contrast, it failed to prevent infection in any of 15 immunized ponies that were challenged with the heterologous PV strain. Levels of PV virus replication and the development of disease, however, were significantly reduced in 12 of the 15 ponies so challenged. The subunit vaccine prevented infection from homologous challenge in four of four ponies tested but failed to prevent infection in all four challenged with the PV strain. Two of the four subunit vaccinates had more severe symptoms of equine infectious anemia than nonimmunized ponies infected in parallel. Both vaccines stimulated EIAV-specific cell-mediated immunity. The in vitro lymphoproliferative response was shown to be mediated by T lymphocytes and appeared to be indistinguishable from that induced by EIAV infection. Significant differences were observed in the in vivo lymphocyte responses following challenge with the two virus strains. While peripheral blood mononuclear cells from the inactivated virus vaccinates were equally stimulated by both the prototype and PV strains, the subunit vaccinates challenged with PV exhibited lower levels of spontaneous proliferation and serine esterase activity. This diminished cellular response to PV was correlated with more severe clinical disease in the same ponies. These studies demonstrate for the first time that both an EIAV inactivated whole-virus vaccine and a viral envelope glycoprotein-based subunit vaccine can provide protection against rigorous challenge levels of homologous virus but are unable to protect against similar challenge levels of a heterologous virus. Moreover, the data demonstrate that protection can be achieved in the absence of detectable levels of virus-specific neutralizing antibody in the vaccine recipients at the time of virus challenge. While vaccine-induced virus-specific cell-mediated immune responses were detected, their role in conferring protection was not obvious. Nevertheless, protection from disease appeared to be correlated with the induction of high levels of serine esterase activity following challenge. A significant observation is that while the whole-virus vaccine was usually capable of preventing or markedly moderating disease in the PV-infected ponies, the subunit vaccine appeared to have a high potential to enhance the disease induced by PV infection.(ABSTRACT TRUNCATED AT 400 WORDS)

Full text

PDF
3398

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Amborski G. F., Jeffers G., Amborski R. L., Issel C. J. Equine infectious anemia virus: development of a simple reproducible method for titrating infectivity of the cell-adapted strain. Am J Vet Res. 1979 Feb;40(2):302–304. [PubMed] [Google Scholar]
  2. Berman P. W., Gregory T. J., Riddle L., Nakamura G. R., Champe M. A., Porter J. P., Wurm F. M., Hershberg R. D., Cobb E. K., Eichberg J. W. Protection of chimpanzees from infection by HIV-1 after vaccination with recombinant glycoprotein gp120 but not gp160. Nature. 1990 Jun 14;345(6276):622–625. doi: 10.1038/345622a0. [DOI] [PubMed] [Google Scholar]
  3. Carlson J. R., McGraw T. P., Keddie E., Yee J. L., Rosenthal A., Langlois A. J., Dickover R., Donovan R., Luciw P. A., Jennings M. B. Vaccine protection of rhesus macaques against simian immunodeficiency virus infection. AIDS Res Hum Retroviruses. 1990 Nov;6(11):1239–1246. doi: 10.1089/aid.1990.6.1239. [DOI] [PubMed] [Google Scholar]
  4. Desrosiers R. C., Wyand M. S., Kodama T., Ringler D. J., Arthur L. O., Sehgal P. K., Letvin N. L., King N. W., Daniel M. D. Vaccine protection against simian immunodeficiency virus infection. Proc Natl Acad Sci U S A. 1989 Aug;86(16):6353–6357. doi: 10.1073/pnas.86.16.6353. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Gerencer M., Valpotić I., Jukić B., Tomasković M., Basić I. Qualitative analyses of cellular immune functions in equine infectious anemia show homology with AIDS. Arch Virol. 1989;104(3-4):249–257. doi: 10.1007/BF01315547. [DOI] [PubMed] [Google Scholar]
  6. Henson J. B., McGuire T. C. Equine infectious anemia. Prog Med Virol. 1974;18(0):143–159. [PubMed] [Google Scholar]
  7. Homsy J., Meyer M., Levy J. A. Serum enhancement of human immunodeficiency virus (HIV) infection correlates with disease in HIV-infected individuals. J Virol. 1990 Apr;64(4):1437–1440. doi: 10.1128/jvi.64.4.1437-1440.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Horohov D. W., Crim J. A., Smith P. L., Siegel J. P. IL-4 (B cell-stimulatory factor 1) regulates multiple aspects of influenza virus-specific cell-mediated immunity. J Immunol. 1988 Dec 15;141(12):4217–4223. [PubMed] [Google Scholar]
  9. Issel C. J., Coggins L. Equine infectious anemia: current knowledge. J Am Vet Med Assoc. 1979 Apr 1;174(7):727–733. [PubMed] [Google Scholar]
  10. Issel C. J., Foil L. D. Studies on equine infectious anemia virus transmission by insects. J Am Vet Med Assoc. 1984 Feb 1;184(3):293–297. [PubMed] [Google Scholar]
  11. Issel C. J., Rushlow K., Foil L. D., Montelaro R. C. A perspective on equine infectious anemia with an emphasis on vector transmission and genetic analysis. Vet Microbiol. 1988 Jul;17(3):251–286. doi: 10.1016/0378-1135(88)90069-7. [DOI] [PubMed] [Google Scholar]
  12. Jolly P. E., Huso D., Hart G., Narayan O. Modulation of lentivirus replication by antibodies. Non-neutralizing antibodies to caprine arthritis-encephalitis virus enhance early stages of infection in macrophages, but do not cause increased production of virions. J Gen Virol. 1989 Aug;70(Pt 8):2221–2226. doi: 10.1099/0022-1317-70-8-2221. [DOI] [PubMed] [Google Scholar]
  13. Knowles D., Jr, Cheevers W., McGuire T., Stem T., Gorham J. Severity of arthritis is predicted by antibody response to gp135 in chronic infection with caprine arthritis-encephalitis virus. J Virol. 1990 May;64(5):2396–2398. doi: 10.1128/jvi.64.5.2396-2398.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Kono Y., Kobayashi K., Fukunaga Y. Antigenic drift of equine infectious anemia virus in chronically infected horses. Arch Gesamte Virusforsch. 1973;41(1):1–10. doi: 10.1007/BF01249923. [DOI] [PubMed] [Google Scholar]
  15. Kono Y., Kobayashi K., Fukunaga Y. Immunization of horses against equine infectious anemia (EIA) with an attenuated EIA virus. Natl Inst Anim Health Q (Tokyo) 1970 Fall;10(3):113–122. [PubMed] [Google Scholar]
  16. Kurth R., Binninger D., Ennen J., Denner J., Hartung S., Norley S. The quest for an AIDS vaccine: the state of the art and current challenges. AIDS Res Hum Retroviruses. 1991 May;7(5):425–433. doi: 10.1089/aid.1991.7.425. [DOI] [PubMed] [Google Scholar]
  17. Malmquist W. A., Barnett D., Becvar C. S. Production of equine infectious anemia antigen in a persistently infected cell line. Arch Gesamte Virusforsch. 1973;42(4):361–370. doi: 10.1007/BF01250717. [DOI] [PubMed] [Google Scholar]
  18. McGuire T. C., Adams D. S., Johnson G. C., Klevjer-Anderson P., Barbee D. D., Gorham J. R. Acute arthritis in caprine arthritis-encephalitis virus challenge exposure of vaccinated or persistently infected goats. Am J Vet Res. 1986 Mar;47(3):537–540. [PubMed] [Google Scholar]
  19. Montefiori D. C., Robinson W. E., Jr, Hirsch V. M., Modliszewski A., Mitchell W. M., Johnson P. R. Antibody-dependent enhancement of simian immunodeficiency virus (SIV) infection in vitro by plasma from SIV-infected rhesus macaques. J Virol. 1990 Jan;64(1):113–119. doi: 10.1128/jvi.64.1.113-119.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Montelaro R. C., Lohrey N., Parekh B., Blakeney E. W., Issel C. J. Isolation and comparative biochemical properties of the major internal polypeptides of equine infectious anemia virus. J Virol. 1982 Jun;42(3):1029–1038. doi: 10.1128/jvi.42.3.1029-1038.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Montelaro R. C., Parekh B., Orrego A., Issel C. J. Antigenic variation during persistent infection by equine infectious anemia virus, a retrovirus. J Biol Chem. 1984 Aug 25;259(16):10539–10544. [PubMed] [Google Scholar]
  22. Montelaro R. C., West M., Issel C. J. Isolation of equine infectious anemia virus glycoproteins. Lectin affinity chromatography procedures for high avidity glycoproteins. J Virol Methods. 1983 Jun;6(6):337–346. doi: 10.1016/0166-0934(83)90056-3. [DOI] [PubMed] [Google Scholar]
  23. Montelaro R., Ball J., Rwambo P., Issel C. Antigenic variation during persistent lentivirus infections and its implications for vaccine development. Adv Exp Med Biol. 1989;251:251–272. doi: 10.1007/978-1-4757-2046-4_24. [DOI] [PubMed] [Google Scholar]
  24. Murphey-Corb M., Martin L. N., Davison-Fairburn B., Montelaro R. C., Miller M., West M., Ohkawa S., Baskin G. B., Zhang J. Y., Putney S. D. A formalin-inactivated whole SIV vaccine confers protection in macaques. Science. 1989 Dec 8;246(4935):1293–1297. doi: 10.1126/science.2555923. [DOI] [PubMed] [Google Scholar]
  25. Murphey-Corb M., Montelaro R. C., Miller M. A., West M., Martin L. N., Davison-Fairburn B., Ohkawa S., Baskin G. B., Zhang J. Y., Miller G. B. Efficacy of SIV/deltaB670 glycoprotein-enriched and glycoprotein-depleted subunit vaccines in protecting against infection and disease in rhesus monkeys. AIDS. 1991 Jun;5(6):655–662. doi: 10.1097/00002030-199106000-00003. [DOI] [PubMed] [Google Scholar]
  26. Nixon D. F., Townsend A. R., Elvin J. G., Rizza C. R., Gallwey J., McMichael A. J. HIV-1 gag-specific cytotoxic T lymphocytes defined with recombinant vaccinia virus and synthetic peptides. Nature. 1988 Dec 1;336(6198):484–487. doi: 10.1038/336484a0. [DOI] [PubMed] [Google Scholar]
  27. O'Rourke K., Perryman L. E., McGuire T. C. Antiviral, anti-glycoprotein and neutralizing antibodies in foals with equine infectious anaemia virus. J Gen Virol. 1988 Mar;69(Pt 3):667–674. doi: 10.1099/0022-1317-69-3-667. [DOI] [PubMed] [Google Scholar]
  28. Payne S. L., Fang F. D., Liu C. P., Dhruva B. R., Rwambo P., Issel C. J., Montelaro R. C. Antigenic variation and lentivirus persistence: variations in envelope gene sequences during EIAV infection resemble changes reported for sequential isolates of HIV. Virology. 1987 Dec;161(2):321–331. doi: 10.1016/0042-6822(87)90124-3. [DOI] [PubMed] [Google Scholar]
  29. Pedersen N. C., Johnson L., Birch D., Theilen G. H. Possible immunoenhancement of persistent viremia by feline leukemia virus envelope glycoprotein vaccines in challenge-exposure situations where whole inactivated virus vaccines were protective. Vet Immunol Immunopathol. 1986 Feb;11(2):123–148. doi: 10.1016/0165-2427(86)90093-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Perryman L. E., O'Rourke K. I., McGuire T. C. Immune responses are required to terminate viremia in equine infectious anemia lentivirus infection. J Virol. 1988 Aug;62(8):3073–3076. doi: 10.1128/jvi.62.8.3073-3076.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Robinson W. E., Jr, Kawamura T., Gorny M. K., Lake D., Xu J. Y., Matsumoto Y., Sugano T., Masuho Y., Mitchell W. M., Hersh E. Human monoclonal antibodies to the human immunodeficiency virus type 1 (HIV-1) transmembrane glycoprotein gp41 enhance HIV-1 infection in vitro. Proc Natl Acad Sci U S A. 1990 Apr;87(8):3185–3189. doi: 10.1073/pnas.87.8.3185. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Rwambo P. M., Issel C. J., Adams W. V., Jr, Hussain K. A., Miller M., Montelaro R. C. Equine infectious anemia virus (EIAV) humoral responses of recipient ponies and antigenic variation during persistent infection. Arch Virol. 1990;111(3-4):199–212. doi: 10.1007/BF01311054. [DOI] [PubMed] [Google Scholar]
  33. Rwambo P. M., Issel C. J., Hussain K. A., Montelaro R. C. In vitro isolation of a neutralization escape mutant of equine infectious anemia virus (EIAV). Arch Virol. 1990;111(3-4):275–280. doi: 10.1007/BF01311062. [DOI] [PubMed] [Google Scholar]
  34. Shively M. A., Banks K. L., Greenlee A., Klevjer-Anderson P. Antigenic stimulation of T lymphocytes in chronic nononcogenic retrovirus infection: equine infectious anemia. Infect Immun. 1982 Apr;36(1):38–46. doi: 10.1128/iai.36.1.38-46.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Stott E. J. Anti-cell antibody in macaques. Nature. 1991 Oct 3;353(6343):393–393. doi: 10.1038/353393a0. [DOI] [PubMed] [Google Scholar]
  36. Welsh R. M., Nishioka W. K., Antia R., Dundon P. L. Mechanism of killing by virus-induced cytotoxic T lymphocytes elicited in vivo. J Virol. 1990 Aug;64(8):3726–3733. doi: 10.1128/jvi.64.8.3726-3733.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Zarling J. M., Morton W., Moran P. A., McClure J., Kosowski S. G., Hu S. L. T-cell responses to human AIDS virus in macaques immunized with recombinant vaccinia viruses. 1986 Sep 25-Oct 1Nature. 323(6086):344–346. doi: 10.1038/323344a0. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Virology are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES