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Journal of virology2005; 79(5); 2666-2677; doi: 10.1128/JVI.79.5.2666-2677.2005

Discerning an effective balance between equine infectious anemia virus attenuation and vaccine efficacy.

Abstract: Among the diverse experimental vaccines evaluated in various animal lentivirus models, live attenuated vaccines have proven to be the most effective, thus providing an important model for examining critical immune correlates of protective vaccine immunity. We previously reported that an experimental live attenuated vaccine for equine infectious anemia virus (EIAV), based on mutation of the viral S2 accessory gene, elicited protection from detectable infection by virulent virus challenge (F. Li et al., J. Virol. 77:7244-7253, 2003). To better understand the critical components of EIAV vaccine efficacy, we examine here the relationship between the extent of virus attenuation, the maturation of host immune responses, and vaccine efficacy in a comparative study of three related attenuated EIAV proviral vaccine strains: the previously described EIAV(UK)DeltaS2 derived from a virulent proviral clone, EIAV(UK)DeltaS2/DU containing a second gene mutation in the virulent proviral clone, and EIAV(PR)DeltaS2 derived from a reference avirulent proviral clone. Inoculations of parallel groups of eight horses resulted in relatively low levels of viral replication (average of 10(2) to 10(3) RNA copies/ml) and a similar maturation of EIAV envelope-specific antibody responses as determined in quantitative and qualitative serological assays. However, experimental challenge of the experimentally immunized horses by our standard virulent EIAV(PV) strain by using a low-dose multiple exposure protocol (three inoculations with 10 median horse infective doses, administered intravenously) revealed a marked difference in the protective efficacy of the various attenuated proviral vaccine strains that was evidently associated with the extent of vaccine virus attenuation, time of viral challenge, and the apparent maturation of virus-specific immunity.
Publication Date: 2005-02-15 PubMed ID: 15708986PubMed Central: PMC548432DOI: 10.1128/JVI.79.5.2666-2677.2005Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't
  • Research Support
  • U.S. Gov't
  • P.H.S.

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research article discusses how a correctly balanced live attenuated vaccine can provide protection against equine infectious anemia virus (EIAV) without causing harmful infection. The researchers examined the relationship between the degree of virus attenuation, the development of host immune responses, and vaccine efficacy.

Objective and Background of the Study

  • The goal of this research was to better comprehend the essential components of EIAV vaccine efficacy. They wanted to determine how the level of virus attenuation (weakening of the virus), the maturation of host immune responses, and vaccine efficacy are linked.
  • Equine infectious anemia virus (EIAV) is a significant disease in horses with live attenuated vaccines being one of the most effective methods to control the disease.
  • The team had previously developed an experimental live attenuated vaccine for EIAV, based on mutation of the viral S2 accessory gene, and found it afforded protection from detectable infection.

Methodology

  • The research compared three related attenuated EIAV proviral vaccine strains: EIAV(UK)DeltaS2, EIAV(UK)DeltaS2/DU, and EIAV(PR)DeltaS2.
  • These vaccines were given to parallel groups of eight horses ensuing in relatively low levels of viral replication and similar maturation of EIAV envelope-specific antibody responses.
  • The immunized horses were later challenged with the EIAV(PV) strain using a low-dose multiple exposure protocol.

Findings and Conclusion

  • The outcomes of the experiment showed a noticeable difference in how the distinct attenuated proviral vaccine strains protected the horses. This variability seemed to be linked to factors such as the degree of vaccine virus attenuation, the timing of the viral challenge, and the maturation of virus-specific immunity.
  • The study concludes that live attenuated vaccines can be effective in preventing EIAV if properly balanced in terms of virus attenuation and the development of a suitable host immune response.

Cite This Article

APA
Craigo JK, Li F, Steckbeck JD, Durkin S, Howe L, Cook SJ, Issel C, Montelaro RC. (2005). Discerning an effective balance between equine infectious anemia virus attenuation and vaccine efficacy. J Virol, 79(5), 2666-2677. https://doi.org/10.1128/JVI.79.5.2666-2677.2005

Publication

ISSN: 0022-538X
NlmUniqueID: 0113724
Country: United States
Language: English
Volume: 79
Issue: 5
Pages: 2666-2677

Researcher Affiliations

Craigo, Jodi K
  • Department of Molecular Genetics and Biochemistry, W1144 Biomedical Science Tower, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.
Li, Feng
    Steckbeck, Jonathan D
      Durkin, Shannon
        Howe, Laryssa
          Cook, Sheila J
            Issel, Charles
              Montelaro, Ronald C

                MeSH Terms

                • Animals
                • Antibodies, Viral / blood
                • Equine Infectious Anemia / immunology
                • Equine Infectious Anemia / prevention & control
                • Equine Infectious Anemia / virology
                • Female
                • Genes, Viral
                • Horses
                • Infectious Anemia Virus, Equine / genetics
                • Infectious Anemia Virus, Equine / immunology
                • Infectious Anemia Virus, Equine / pathogenicity
                • Male
                • Mutation
                • Time Factors
                • Vaccines, Attenuated / genetics
                • Vaccines, Attenuated / pharmacology
                • Viral Proteins / genetics
                • Viral Proteins / immunology
                • Viral Vaccines / genetics
                • Viral Vaccines / pharmacology

                Grant Funding

                • R01 AI025850 / NIAID NIH HHS
                • R01 AI25850 / NIAID NIH HHS

                References

                This article includes 39 references
                1. Bogers WM, Cheng-Mayer C, Montelaro RC. Developments in preclinical AIDS vaccine efficacy models.. AIDS 2000;14 Suppl 3:S141-51.
                  pubmed: 11086857
                2. Coggins L, Norcross NL. Immunodiffusion reaction in equine infectious anemia.. Cornell Vet 1970 Apr;60(2):330-5.
                  pubmed: 4986043
                3. Cole KS, Rowles JL, Jagerski BA, Murphey-Corb M, Unangst T, Clements JE, Robinson J, Wyand MS, Desrosiers RC, Montelaro RC. 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 1997 Jul;71(7):5069-79.
                4. Cole KS, Rowles JL, Murphey-Corb M, Clements JE, Robinson J, Montelaro RC. A model for the maturation of protective antibody responses to SIV envelope proteins in experimentally immunized monkeys.. J Med Primatol 1997 Feb-Apr;26(1-2):51-8.
                5. Cole KS, Murphey-Corb M, Narayan O, Joag SV, Shaw GM, Montelaro RC. Common themes of antibody maturation to simian immunodeficiency virus, simian-human immunodeficiency virus, and human immunodeficiency virus type 1 infections.. J Virol 1998 Oct;72(10):7852-9.
                6. Cook RF, Leroux C, Cook SJ, Berger SL, Lichtenstein DL, Ghabrial NN, Montelaro RC, Issel CJ. Development and characterization of an in vivo pathogenic molecular clone of equine infectious anemia virus.. J Virol 1998 Feb;72(2):1383-93.
                7. Craigo JK, Leroux C, Howe L, Steckbeck JD, Cook SJ, Issel CJ, Montelaro RC. 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 2002 Jun;83(Pt 6):1353-1359.
                  pubmed: 12029150doi: 10.1099/0022-1317-83-6-1353google scholar: lookup
                8. Grund CH, Lechman ER, Issel CJ, Montelaro RC, Rushlow KE. Lentivirus cross-reactive determinants present in the capsid protein of equine infectious anaemia virus.. J Gen Virol 1994 Mar;75 ( Pt 3):657-62.
                  pubmed: 7510329doi: 10.1099/0022-1317-75-3-657google scholar: lookup
                9. Hammond SA, Cook SJ, Falo LD Jr, Issel CJ, Montelaro RC. A particulate viral protein vaccine reduces viral load and delays progression to disease in immunized ponies challenged with equine infectious anemia virus.. Virology 1999 Feb 1;254(1):37-49.
                  pubmed: 9927572doi: 10.1006/viro.1998.9550google scholar: lookup
                10. Hammond SA, Cook SJ, Lichtenstein DL, Issel CJ, Montelaro RC. 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 1997 May;71(5):3840-52.
                11. Hammond SA, Li F, McKeon BM Sr, Cook SJ, Issel CJ, Montelaro RC. Immune responses and viral replication in long-term inapparent carrier ponies inoculated with equine infectious anemia virus.. J Virol 2000 Jul;74(13):5968-81.
                12. Hammond SA, Raabe ML, Issel CJ, Montelaro RC. Evaluation of antibody parameters as potential correlates of protection or enhancement by experimental vaccines to equine infectious anemia virus.. Virology 1999 Sep 30;262(2):416-30.
                  pubmed: 10502520doi: 10.1006/viro.1999.9939google scholar: lookup
                13. Harrold SM, Cook SJ, Cook RF, Rushlow KE, Issel CJ, Montelaro RC. Tissue sites of persistent infection and active replication of equine infectious anemia virus during acute disease and asymptomatic infection in experimentally infected equids.. J Virol 2000 Apr;74(7):3112-21.
                14. Issel CJ, Horohov DW, Lea DF, Adams WV Jr, Hagius SD, McManus JM, Allison AC, Montelaro RC. Efficacy of inactivated whole-virus and subunit vaccines in preventing infection and disease caused by equine infectious anemia virus.. J Virol 1992 Jun;66(6):3398-408.
                15. Johnson RP, Desrosiers RC. Protective immunity induced by live attenuated simian immunodeficiency virus.. Curr Opin Immunol 1998 Aug;10(4):436-43.
                  pubmed: 9722920doi: 10.1016/s0952-7915(98)80118-0google scholar: lookup
                16. Johnson RP, Lifson JD, Czajak SC, Cole KS, Manson KH, Glickman R, Yang J, Montefiori DC, Montelaro R, Wyand MS, Desrosiers RC. Highly attenuated vaccine strains of simian immunodeficiency virus protect against vaginal challenge: inverse relationship of degree of protection with level of attenuation.. J Virol 1999 Jun;73(6):4952-61.
                17. Leroux C, Issel CJ, Montelaro RC. Novel and dynamic evolution of equine infectious anemia virus genomic quasispecies associated with sequential disease cycles in an experimentally infected pony.. J Virol 1997 Dec;71(12):9627-39.
                18. Li F, Leroux C, Craigo JK, Cook SJ, Issel CJ, Montelaro RC. The S2 gene of equine infectious anemia virus is a highly conserved determinant of viral replication and virulence properties in experimentally infected ponies.. J Virol 2000 Jan;74(1):573-9.
                19. Li F, Puffer BA, Montelaro RC. The S2 gene of equine infectious anemia virus is dispensable for viral replication in vitro.. J Virol 1998 Oct;72(10):8344-8.
                20. Li F, Craigo JK, Howe L, Steckbeck JD, Cook S, Issel C, Montelaro RC. 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 2003 Jul;77(13):7244-53.
                21. Lichtenstein DL, Issel CJ, Montelaro RC. Genomic quasispecies associated with the initiation of infection and disease in ponies experimentally infected with equine infectious anemia virus.. J Virol 1996 Jun;70(6):3346-54.
                22. Lichtenstein DL, Rushlow KE, Cook RF, Raabe ML, Swardson CJ, Kociba GJ, Issel CJ, Montelaro RC. Replication in vitro and in vivo of an equine infectious anemia virus mutant deficient in dUTPase activity.. J Virol 1995 May;69(5):2881-8.
                23. Lockridge KM, Chien M, Dean GA, Stefano Cole K, Montelaro RC, Luciw PA, Sparger EE. Protective immunity against feline immunodeficiency virus induced by inoculation with vif-deleted proviral DNA.. Virology 2000 Jul 20;273(1):67-79.
                  pubmed: 10891409doi: 10.1006/viro.2000.0395google scholar: lookup
                24. Maniatis T, Fritsch EF, Sambrook JE. Molecular cloning: a laboratory manual, 2nd ed.. 1982.
                25. Mills J, Desrosiers R, Rud E, Almond N. Live attenuated HIV vaccines: a proposal for further research and development.. AIDS Res Hum Retroviruses 2000 Oct 10;16(15):1453-61.
                  pubmed: 11054258doi: 10.1089/088922200750005976google scholar: lookup
                26. Montelaro RC, Ball JM, Rushlow K. Equine retroviruses. 1993;p. 257-360.
                27. Montelaro RC, Cole KS, Hammond SA. Maturation of immune responses to lentivirus infection: implications for AIDS vaccine development.. AIDS Res Hum Retroviruses 1998 Oct;14 Suppl 3:S255-9.
                  pubmed: 9814952
                28. Montelaro RC, Grund C, Raabe M, Woodson B, Cook RF, Cook S, Issel CJ. Characterization of protective and enhancing immune responses to equine infectious anemia virus resulting from experimental vaccines.. AIDS Res Hum Retroviruses 1996 Mar 20;12(5):413-5.
                  pubmed: 8882322doi: 10.1089/aid.1996.12.413google scholar: lookup
                29. Nilsson C, Mäkitalo B, Thorstensson R, Norley S, Binninger-Schinzel D, Cranage M, Rud E, Biberfeld G, Putkonen P. Live attenuated simian immunodeficiency virus (SIV)mac in macaques can induce protection against mucosal infection with SIVsm.. AIDS 1998 Dec 3;12(17):2261-70.
                30. Payne SL, Rausch J, Rushlow K, Montelaro RC, Issel C, Flaherty M, Perry S, Sellon D, Fuller F. Characterization of infectious molecular clones of equine infectious anaemia virus.. J Gen Virol 1994 Feb;75 ( Pt 2):425-9.
                  pubmed: 8113766doi: 10.1099/0022-1317-75-2-425google scholar: lookup
                31. Raabe ML, Issel CJ, Cook SJ, Cook RF, Woodson B, Montelaro RC. 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 1998 May 25;245(1):151-62.
                  pubmed: 9614876doi: 10.1006/viro.1998.9142google scholar: lookup
                32. Raabe ML, Issel CJ, Montelaro RC. In vitro antibody-dependent enhancement assays are insensitive indicators of in vivo vaccine enhancement of equine infectious anemia virus.. Virology 1999 Jul 5;259(2):416-27.
                  pubmed: 10388665doi: 10.1006/viro.1999.9772google scholar: lookup
                33. Rwambo PM, Issel CJ, Adams WV Jr, Hussain KA, Miller M, Montelaro RC. Equine infectious anemia virus (EIAV) humoral responses of recipient ponies and antigenic variation during persistent infection.. Arch Virol 1990;111(3-4):199-212.
                  pubmed: 2162160doi: 10.1007/bf01311054google scholar: lookup
                34. Shen R-X, Wang Z. Development and use of an equine infectious anemia donkey leucocyte attenuated vaccine. 1985.
                35. Threadgill DS, Steagall WK, Flaherty MT, Fuller FJ, Perry ST, Rushlow KE, Le Grice SF, Payne SL. Characterization of equine infectious anemia virus dUTPase: growth properties of a dUTPase-deficient mutant.. J Virol 1993 May;67(5):2592-600.
                36. Ui M, Kuwata T, Igarashi T, Ibuki K, Miyazaki Y, Kozyrev IL, Enose Y, Shimada T, Uesaka H, Yamamoto H, Miura T, Hayami M. Protection of macaques against a SHIV with a homologous HIV-1 Env and a pathogenic SHIV-89.6P with a heterologous Env by vaccination with multiple gene-deleted SHIVs.. Virology 1999 Dec 20;265(2):252-63.
                  pubmed: 10600597doi: 10.1006/viro.1999.0049google scholar: lookup
                37. Wyand MS, Manson KH, Garcia-Moll M, Montefiori D, Desrosiers RC. Vaccine protection by a triple deletion mutant of simian immunodeficiency virus.. J Virol 1996 Jun;70(6):3724-33.
                38. Wyand MS, Manson K, Montefiori DC, Lifson JD, Johnson RP, Desrosiers RC. Protection by live, attenuated simian immunodeficiency virus against heterologous challenge.. J Virol 1999 Oct;73(10):8356-63.
                39. Zheng YH, Sentsui H, Nakaya T, Kono Y, Ikuta K. In vivo dynamics of equine infectious anemia viruses emerging during febrile episodes: insertions/duplications at the principal neutralizing domain.. J Virol 1997 Jul;71(7):5031-9.

                Citations

                This article has been cited 15 times.
                1. Hull-Nye D, Meadows T, Smith SR, Schwartz EJ. Key Factors and Parameter Ranges for Immune Control of Equine Infectious Anemia Virus Infection.. Viruses 2023 Mar 6;15(3).
                  doi: 10.3390/v15030691pubmed: 36992401google scholar: lookup
                2. Brocca-Cofano E, Kuhrt D, Siewe B, Xu C, Haret-Richter GS, Craigo J, Labranche C, Montefiori DC, Landay A, Apetrei C, Pandrea I. Pathogenic Correlates of Simian Immunodeficiency Virus-Associated B Cell Dysfunction.. J Virol 2017 Dec 1;91(23).
                  doi: 10.1128/JVI.01051-17pubmed: 28931679google scholar: lookup
                3. Cervantes DT, Ball JM, Edwards J, Payne S. Horses naturally infected with EIAV harbor 2 distinct SU populations but are monophyletic with respect to IN.. Virus Genes 2016 Feb;52(1):71-80.
                  doi: 10.1007/s11262-015-1280-zpubmed: 26739458google scholar: lookup
                4. Craigo JK, Ezzelarab C, Cook SJ, Liu C, Horohov D, Issel CJ, Montelaro RC. Protective efficacy of centralized and polyvalent envelope immunogens in an attenuated equine lentivirus vaccine.. PLoS Pathog 2015 Jan;11(1):e1004610.
                  doi: 10.1371/journal.ppat.1004610pubmed: 25569288google scholar: lookup
                5. Liu C, Cook SJ, Craigo JK, Cook FR, Issel CJ, Montelaro RC, Horohov DW. Epitope shifting of gp90-specific cellular immune responses in EIAV-infected ponies.. Vet Immunol Immunopathol 2014 Oct 15;161(3-4):161-9.
                  doi: 10.1016/j.vetimm.2014.08.001pubmed: 25176006google scholar: lookup
                6. Craigo JK, Montelaro RC. Lessons in AIDS vaccine development learned from studies of equine infectious, anemia virus infection and immunity.. Viruses 2013 Dec 2;5(12):2963-76.
                  doi: 10.3390/v5122963pubmed: 24316675google scholar: lookup
                7. Craigo JK, Ezzelarab C, Cook SJ, Chong L, Horohov D, Issel CJ, Montelaro RC. Envelope determinants of equine lentiviral vaccine protection.. PLoS One 2013;8(6):e66093.
                  doi: 10.1371/journal.pone.0066093pubmed: 23785473google scholar: lookup
                8. Meng Q, Lin Y, Ma J, Ma Y, Zhao L, Li S, Yang K, Zhou J, Shen R, Zhang X, Shao Y. A pilot study comparing the development of EIAV Env-specific antibodies induced by DNA/recombinant vaccinia-vectored vaccines and an attenuated Chinese EIAV vaccine.. Viral Immunol 2012 Dec;25(6):477-84.
                  doi: 10.1089/vim.2012.0014pubmed: 23171359google scholar: lookup
                9. Craigo JK, Ezzelarab C, Montelaro RC. Development of a high throughput, semi-automated, infectious center cell-based ELISA for equine infectious anemia virus.. J Virol Methods 2012 Nov;185(2):221-7.
                10. Craigo JK, Barnes S, Cook SJ, Issel CJ, Montelaro RC. Divergence, not diversity of an attenuated equine lentivirus vaccine strain correlates with protection from disease.. Vaccine 2010 Nov 29;28(51):8095-104.
                  doi: 10.1016/j.vaccine.2010.10.003pubmed: 20955830google scholar: lookup
                11. Craigo JK, Barnes S, Zhang B, Cook SJ, Howe L, Issel CJ, Montelaro RC. An EIAV field isolate reveals much higher levels of subtype variability than currently reported for the equine lentivirus family.. Retrovirology 2009 Oct 20;6:95.
                  doi: 10.1186/1742-4690-6-95pubmed: 19843328google scholar: lookup
                12. Patel JR, Heldens JG. Immunoprophylaxis against important virus disease of horses, farm animals and birds.. Vaccine 2009 Mar 13;27(12):1797-1810.
                  doi: 10.1016/j.vaccine.2008.12.063pubmed: 19402200google scholar: lookup
                13. Craigo JK, Zhang B, Barnes S, Tagmyer TL, Cook SJ, Issel CJ, Montelaro RC. Envelope variation as a primary determinant of lentiviral vaccine efficacy.. Proc Natl Acad Sci U S A 2007 Sep 18;104(38):15105-10.
                  doi: 10.1073/pnas.0706449104pubmed: 17846425google scholar: lookup
                14. Craigo JK, Durkin S, Sturgeon TJ, Tagmyer T, Cook SJ, Issel CJ, Montelaro RC. Immune suppression of challenged vaccinates as a rigorous assessment of sterile protection by lentiviral vaccines.. Vaccine 2007 Jan 15;25(5):834-45.
                  doi: 10.1016/j.vaccine.2006.09.040pubmed: 17023099google scholar: lookup
                15. Steckbeck JD, Grieser HJ, Sturgeon T, Taber R, Chow A, Bruno J, Murphy-Corb M, Montelaro RC, Cole KS. Dynamic evolution of antibody populations in a rhesus macaque infected with attenuated simian immunodeficiency virus identified by surface plasmon resonance.. J Med Primatol 2006 Aug;35(4-5):248-60.