Journal article
Selection of a rare neutralization-resistant variant following passive transfer of convalescent immune plasma in equine infectious anemia virus-challenged SCID horses
Journal of virology, Vol.84(13), pp.6536-6548
07/2010
Handle:
https://hdl.handle.net/2376/108067
PMCID: PMC2903280
PMID: 20392850
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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Details
- Title
- Selection of a rare neutralization-resistant variant following passive transfer of convalescent immune plasma in equine infectious anemia virus-challenged SCID horses
- Creators
- Sandra D Taylor - Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, WA 99164-7040, USASteven R LeibSusan CarpenterRobert H Mealey
- Publication Details
- Journal of virology, Vol.84(13), pp.6536-6548
- Academic Unit
- Veterinary Clinical Sciences, Department of
- Publisher
- United States
- Grant note
- T32 AI007025 / NIAID NIH HHS CA128568 / NCI NIH HHS K02 AI073101 / NIAID NIH HHS AI073101 / NIAID NIH HHS R01 CA128568 / NCI NIH HHS
- Identifiers
- 99900547211601842
- Language
- English
- Resource Type
- Journal article