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PloS one2013; 8(6); e66093; doi: 10.1371/journal.pone.0066093

Envelope determinants of equine lentiviral vaccine protection.

Abstract: Lentiviral envelope (Env) antigenic variation and associated immune evasion present major obstacles to vaccine development. The concept that Env is a critical determinant for vaccine efficacy is well accepted, however defined correlates of protection associated with Env variation have yet to be determined. We reported an attenuated equine infectious anemia virus (EIAV) vaccine study that directly examined the effect of lentiviral Env sequence variation on vaccine efficacy. The study identified a significant, inverse, linear correlation between vaccine efficacy and increasing divergence of the challenge virus Env gp90 protein compared to the vaccine virus gp90. The report demonstrated approximately 100% protection of immunized ponies from disease after challenge by virus with a homologous gp90 (EV0), and roughly 40% protection against challenge by virus (EV13) with a gp90 13% divergent from the vaccine strain. In the current study we examine whether the protection observed when challenging with the EV0 strain could be conferred to animals via chimeric challenge viruses between the EV0 and EV13 strains, allowing for mapping of protection to specific Env sequences. Viruses containing the EV13 proviral backbone and selected domains of the EV0 gp90 were constructed and in vitro and in vivo infectivity examined. Vaccine efficacy studies indicated that homology between the vaccine strain gp90 and the N-terminus of the challenge strain gp90 was capable of inducing immunity that resulted in significantly lower levels of post-challenge virus and significantly delayed the onset of disease. However, a homologous N-terminal region alone inserted in the EV13 backbone could not impart the 100% protection observed with the EV0 strain. Data presented here denote the complicated and potentially contradictory relationship between in vitro virulence and in vivo pathogenicity. The study highlights the importance of structural conformation for immunogens and emphasizes the need for antibody binding, not neutralizing, assays that correlate with vaccine protection.
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Publication Date: 2013-06-13 PubMed ID: 23785473PubMed Central: PMC3682429DOI: 10.1371/journal.pone.0066093Google 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 study examines how variations in the envelope (Env) protein of the equine infectious anemia virus (EIAV) affect the effectiveness of a vaccine. The researchers found a correlation between the divergence in the Env protein of the challenge virus and the vaccine virus, and the efficacy of the vaccine. The study also found that matching specific sequences in the Env protein could induce an immune response, but this alone was not enough to provide full protection. The research suggests the importance of structural stability in vaccine design and the need for assays that correlate with vaccine protection.

Understanding the Impact of Lentiviral Envelope Variation on Vaccine Efficacy

  • The study tries to understand the influence of the Lentiviral envelope (Env) antigenic variation on the effectiveness of a vaccine. This protein has been recognized as a key determinant in the success of a vaccine, but understanding its role more clearly can help in the creation of more effective vaccines.
  • A correlation was found between the variance in the Env protein of the EIAV and the efficacy of the vaccine. It was found that the more the Env protein of the virus being tested differed from that of the vaccine, the lower the efficacy of the vaccine.

Understanding the Role of Specific Env Sequences

  • The study broke down the Env protein into specific sequences to understand if certain sequences played more of a role than others in inducing immunity.
  • They found that homology between the N-terminus of the challenge strain gp90 and the vaccine’s gp90 protein could stimulate immunity.
  • This immunity leads to significantly lower levels of the virus post-challenge, and also significantly delays the onset of disease.
  • However, the study also found that the N-terminal region alone, when inserted into another virus backbone, was not enough to confer 100% protection, unlike the protection observed with the EV0 strain, indicating the complexity of immune response generation.

Implications for Vaccine Design

  • The study suggests the importance of the structural conformation of immunogens, the parts of the vaccine that stimulate an immune response.
  • This suggests that future vaccines might have to pay more attention to the structure of the immunogens, and not simply their presence.
  • Furthermore, the study also emphasized the need for binding assays, as opposed to neutralization assays, which can correlate with vaccine protection, an important aspect for vaccine evaluation and improvements.

Cite This Article

APA
Craigo JK, Ezzelarab C, Cook SJ, Chong L, Horohov D, Issel CJ, Montelaro RC. (2013). Envelope determinants of equine lentiviral vaccine protection. PLoS One, 8(6), e66093. https://doi.org/10.1371/journal.pone.0066093

Publication

PloS one
ISSN: 1932-6203
NlmUniqueID: 101285081
Country: United States
Language: English
Volume: 8
Issue: 6
Pages: e66093
PII: e66093

Researcher Affiliations

Craigo, Jodi K
  • Center for Vaccine Research, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America. craigoj@pitt.edu
Ezzelarab, Corin
    Cook, Sheila J
      Chong, Liu
        Horohov, David
          Issel, Charles J
            Montelaro, Ronald C

              MeSH Terms

              • Animals
              • Cell Line
              • Equine Infectious Anemia / immunology
              • Equine Infectious Anemia / prevention & control
              • Equine Infectious Anemia / virology
              • Gene Order
              • Genome, Viral
              • Horses
              • Immunity, Cellular
              • Immunity, Humoral
              • Infectious Anemia Virus, Equine / genetics
              • Infectious Anemia Virus, Equine / immunology
              • Infectious Anemia Virus, Equine / pathogenicity
              • Proviruses / genetics
              • Recombination, Genetic
              • Viral Envelope Proteins / genetics
              • Viral Envelope Proteins / immunology
              • Viral Load
              • Viral Vaccines / genetics
              • Viral Vaccines / immunology
              • Virulence / genetics

              Grant Funding

              • R01 AI025850 / NIAID NIH HHS
              • UL1 TR000005 / NCATS NIH HHS
              • R01 AI25850 / NIAID NIH HHS

              Conflict of Interest Statement

              The authors have declared that no competing interests exist.

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              Citations

              This article has been cited 4 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).
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              4. Wang XF, Wang S, Liu Q, Lin YZ, Du C, Tang YD, Na L, Wang X, Zhou JH. A unique evolution of the s2 gene of equine infectious anemia virus in hosts correlated with particular infection statuses. Viruses 2014 Nov 10;6(11):4265-79.
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