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Home / Equine Research Bank / J Virol / Selection of a rare neutralization-resistant variant followi...
Journal of virology2010; 84(13); 6536-6548; doi: 10.1128/JVI.00218-10

Selection of a rare neutralization-resistant variant following passive transfer of convalescent immune plasma in equine infectious anemia virus-challenged SCID horses.

Abstract: Vaccines preventing HIV-1 infection will likely elicit antibodies that neutralize diverse strains. However, the capacity for lentiviruses to escape broadly neutralizing antibodies (NAbs) is not completely understood, nor is it known whether NAbs alone can control heterologous infection. Here, we determined that convalescent immune plasma from a horse persistently infected with equine infectious anemia virus (EIAV) neutralized homologous virus and several envelope variants containing heterologous principal neutralizing domains (PND). Plasma was infused into young horses (foals) affected with severe combined immunodeficiency (SCID), followed by challenge with a homologous EIAV stock. Treated SCID foals were protected against clinical disease, with complete prevention of infection occurring in one foal. In three SCID foals, a novel neutralization-resistant variant arose that was found to preexist at a low frequency in the challenge inoculum. In contrast, SCID foals infused with nonimmune plasma developed acute disease associated with high levels of the predominant challenge virus. Following transfer to an immunocompetent horse, the neutralization-resistant variant induced a single febrile episode and was subsequently controlled in the absence of type-specific NAb. Long-term control was associated with the presence of cytotoxic T lymphocytes (CTL). Our results demonstrate that immune plasma with neutralizing activity against heterologous PND variants can prevent lentivirus infection and clinical disease in the complete absence of T cells. Importantly, however, rare neutralization-resistant envelope variants can replicate in vivo under relatively broad selection pressure, highlighting the need for protective lentivirus vaccines to elicit NAb responses with increased breadth and potency and/or CTL that target conserved epitopes.
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Publication Date: 2010-04-14 PubMed ID: 20392850PubMed Central: PMC2903280DOI: 10.1128/JVI.00218-10Google 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.

The researchers in this study are trying to understand how lentiviruses, like HIV-1, can evade the immune system. They use horse models to study this and find that immune plasma can prevent infection and disease. However, they also identify a rare variation of the virus that is resistant to this neutralization, pointing to the need for stronger, more varied immune responses in future vaccines.

Investigation of immune plasma on virus neutralization

  • The researchers work with equine infectious anemia virus (EIAV), which is a lentivirus similar to HIV-1 infecting horses.
  • In their experiment, they take plasma from a horse that has previously been infected with EIAV. This plasma has developed neutralizing antibodies against the disease.
  • They then introduce this immune plasma to young horses who are affected with severe combined immunodeficiency (SCID), which means they have a weakened immune system and are vulnerable to infection.
  • The plasma was found to neutralize the EIAV virus and even some altered versions of it. This prevented the young horses from getting sick.
  • Interestingly, the scientists found that one variant of the virus was resistant to this neutralization and was able to survive and keep replicating.

Evidence of neutralization-resistant virus variant

  • This neutralization-resistant variant was found to exist at a low frequency in the population of viruses used in the experiment.
  • When the neutralization-resistant variant was transferred to a healthy horse with a normal immune system, it only caused a single fever episode before being controlled by the immune system.
  • Long-term control of the virus was associated with the presence of cytotoxic T lymphocytes (CTL), a type of immune cell.

Implication for future vaccine development

  • This research suggests that any vaccine against lentiviruses needs to be able to generate a broad and potent neutralizing antibody response. This is necessary to be able to neutralize most variations of the virus.
  • Additionally, the findings show the importance of stimulating a cytotoxic T lymphocyte (CTL) response as part of the vaccine since CTL was shown to be able to control a neutralization-resistant virus variant.
  • This research indicates the complexity of vaccine development for viruses like HIV-1, which are able to mutate and develop resistance to the immune response.

Cite This Article

APA
Taylor SD, Leib SR, Carpenter S, Mealey RH. (2010). Selection of a rare neutralization-resistant variant following passive transfer of convalescent immune plasma in equine infectious anemia virus-challenged SCID horses. J Virol, 84(13), 6536-6548. https://doi.org/10.1128/JVI.00218-10

Publication

Journal of virology
ISSN: 1098-5514
NlmUniqueID: 0113724
Country: United States
Language: English
Volume: 84
Issue: 13
Pages: 6536-6548

Researcher Affiliations

Taylor, Sandra D
  • Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, WA 99164-7040, USA.
Leib, Steven R
    Carpenter, Susan
      Mealey, Robert H

        MeSH Terms

        • Animals
        • Antibodies, Neutralizing / immunology
        • Antibodies, Viral / immunology
        • Equine Infectious Anemia / immunology
        • Horses
        • Immune Sera / immunology
        • Infectious Anemia Virus, Equine / genetics
        • Infectious Anemia Virus, Equine / immunology
        • Severe Combined Immunodeficiency / complications
        • T-Lymphocytes, Cytotoxic / immunology

        Grant Funding

        • K02 AI073101 / NIAID NIH HHS
        • T32 AI007025 / NIAID NIH HHS
        • R01 CA128568 / NCI NIH HHS
        • AI073101 / NIAID NIH HHS
        • CA128568 / NCI NIH HHS

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        Citations

        This article has been cited 10 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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