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Home / Equine Research Bank / J Virol / Envelope determinants of equine infectious anemia virus vacc...
Journal of virology2008; 82(8); 4052-4063; doi: 10.1128/JVI.02028-07

Envelope determinants of equine infectious anemia virus vaccine protection and the effects of sequence variation on immune recognition.

Abstract: A highly effective attenuated equine infectious anemia virus (EIAV) vaccine (EIAV(D9)) capable of protecting 100% of horses from disease induced by a homologous Env challenge strain (EIAV(PV)) was recently tested in ponies to determine the level of protection against divergent Env challenge strains (J. K. Craigo, B. S. Zhang, S. Barnes, T. L. Tagmyer, S. J. Cook, C. J. Issel, and R. C. Montelaro, Proc. Natl. Acad. Sci. USA 104:15105-15110, 2007). An inverse correlation between challenge strain Env variation and vaccine protection from disease was observed. Given the striking differences in protective immunity, we hypothesized that analysis of the humoral and cellular immune responses to the Env protein could reveal potential determinants of vaccine protection. Neutralization activity against the homologous Env or challenge strain-specific Env in immune sera from the vaccinated ponies did not correlate with protection from disease. Cellular analysis with Env peptide pools did not reveal an association with vaccine protection from disease. However, when individual vaccine-specific Env peptides were utilized, eight cytotoxic-T-lymphocyte (CTL) peptides were found to associate closely with vaccine protection. One of these peptides also yielded the only lymphoproliferative response associated with protective immunity. The identified peptides spanned both variable and conserved regions of gp90. Amino acid divergence within the principal neutralization domain and the identified peptides profoundly affected immune recognition, as illustrated by the inability to detect cross-reactive neutralizing antibodies and the observation that certain peptide-specific CTL responses were altered. In addition to identifying potential Env determinants of EIAV vaccine efficacy and demonstrating the profound effects of defined Env variation on immune recognition, these data also illustrate the sensitivity offered by individual peptides compared to peptide pools in measuring cellular immune responses in lentiviral vaccine trials.
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Publication Date: 2008-01-30 PubMed ID: 18234792PubMed Central: PMC2292999DOI: 10.1128/JVI.02028-07Google Scholar: Lookup
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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.

This research explores how the effectiveness of a specific vaccine for equine infectious anemia virus (EIAV) is influenced by variations in certain parts of the EIAV virus itself. It also provides insights into how these variations impact the recognition of the virus by the immune system.

Research Context and Objectives

  • The focus of the research was on a highly effective EIAV vaccine (referred to as EIAV(D9)) which has been shown to protect 100% of horses from disease triggered by a type of the virus that matches with the version used in the vaccine (Env challenge strain EIAV(PV)).
  • A previous experiment tested how this vaccine performs when used to protect against different versions of the virus (divergent Env challenge strains).
  • The researchers noticed a pattern: the more different a challenge strain was from the version used in the vaccine, the less effective the vaccine was at protecting against disease caused by that strain.
  • Based upon these findings, the researchers hypothesized that studying immunity responses to an EIAV protein (known as Env) might reveal clues about what makes the vaccine more or less effective.

Research Methodology and Findings

  • The researchers carried out a detailed analysis of the immune responses in horses (ponies, specifically) that had been vaccinated using the EIAV(D9) vaccine.
  • They found that the presence of neutralizing activity against the virus in the immune serum of the ponies didn’t correlate with protection from the disease. Essentially, just because a pony’s bodily fluids could neutralize the virus didn’t mean that it was protected from falling ill.
  • Furthermore, analyzing the immune responses at a ‘cellular’ level didn’t shed much light on the protective effectiveness of the vaccine, that is, until the researchers started looking at the immune responses to individual peptides (smaller chunks of proteins).
  • Analysing the peptides one by one, eight specific peptides were closely associated with effective vaccine protection.
  • One particular peptide also prompted the single lymphoproliferative response that was linked with protective immunity. Lymphoproliferative responses are part of how the immune system reacts to infection or disease, particularly diseases involving white blood cells (lymphocytes).

Conclusions and Implications

  • The research identified which parts of the EIAV virus might be chiefly responsible for determining how well the EIAV(D9) vaccine works.
  • Differences in the identified peptides had a profound effect on the immune system’s recognition of the virus.
  • The researchers concluded that individual peptides provide more sensitive measures of cellular immune responses in vaccine trials for lentiviruses (a group of viruses that includes HIV).
  • This work contributes to our understanding of how vaccines for lentiviruses work, and how variations in the virus can make the vaccine more or less effective.

Cite This Article

APA
Tagmyer TL, Craigo JK, Cook SJ, Even DL, Issel CJ, Montelaro RC. (2008). Envelope determinants of equine infectious anemia virus vaccine protection and the effects of sequence variation on immune recognition. J Virol, 82(8), 4052-4063. https://doi.org/10.1128/JVI.02028-07

Publication

Journal of virology
ISSN: 1098-5514
NlmUniqueID: 0113724
Country: United States
Language: English
Volume: 82
Issue: 8
Pages: 4052-4063

Researcher Affiliations

Tagmyer, Tara L
  • E1240 Biomedical Science Tower, Department of Microbiology and Molecular Genetics, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15261, USA.
Craigo, Jodi K
    Cook, Sheila J
      Even, Deborah L
        Issel, Charles J
          Montelaro, Ronald C

            MeSH Terms

            • Animals
            • Antibodies, Viral / blood
            • Cell Proliferation
            • Cytotoxicity Tests, Immunologic
            • Epitopes / genetics
            • Epitopes / immunology
            • Equine Infectious Anemia / prevention & control
            • Horses
            • Infectious Anemia Virus, Equine / immunology
            • Leukocytes, Mononuclear / immunology
            • Neutralization Tests
            • Peptides / immunology
            • Viral Envelope Proteins / genetics
            • Viral Envelope Proteins / immunology
            • Viral Vaccines / immunology

            Grant Funding

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

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