Pre-existing neutralizing antibody mitigates B cell dysregulation and enhances the Envspecific antibody response in SHIV-infected rhesus macaques

Juan Pablo Jaworski, Peter Bryk, Zachary Brower, Bo Zheng, Ann Hessell, Alexander F. Rosenberg, Tong Tong Wu, Ignacio Sanz, Michael C. Keefer, Nancy Haigwood, James J. Kobie

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    2 Scopus citations

    Abstract

    Our central hypothesis is that protection against HIV infection will be powerfully influenced by the magnitude and quality of the B cell response. Although sterilizing immunity, mediated by pre-formed abundant and potent antibodies is the ultimate goal for B cell-targeted HIV vaccine strategies, scenarios that fall short of this may still confer beneficial defenses against viremia and disease progression. We evaluated the impact of sub-sterilizing pre-existing neutralizing antibody on the B cell response to SHIV infection. Adult male rhesus macaques received passive transfer of a sub-sterilizing amount of polyclonal neutralizing immunoglobulin (Ig) purified from previously infected animals (SHIVIG) or control Ig prior to intra-rectal challenge with SHIVSF162P4 and extensive longitudinal sampling was performed. SHIVIG treated animals exhibited significantly reduced viral load and increased de novo Env-specific plasma antibody. Dysregulation of the B cell profile was grossly apparent soon after infection in untreated animals; exemplified by a ≈50% decrease in total B cells in the blood evident 2-3 weeks postinfection which was not apparent in SHIVIG treated animals. IgD+CD5+CD21+ B cells phenotypically similar to marginal zone-like B cells were highly sensitive to SHIV infection, becoming significantly decreased as early as 3 days post-infection in control animals, while being maintained in SHIVIG treated animals, and were highly correlated with the induction of Env-specific plasma antibody. These results suggest that B cell dysregulation during the early stages of infection likely contributes to suboptimal Env-specific B cell and antibody responses, and strategies that limit this dysregulation may enhance the host's ability to eliminate HIV.

    Original languageEnglish (US)
    Article numbere0172524
    JournalPLoS One
    Volume12
    Issue number2
    DOIs
    StatePublished - Feb 1 2017

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    ASJC Scopus subject areas

    • Medicine(all)
    • Biochemistry, Genetics and Molecular Biology(all)
    • Agricultural and Biological Sciences(all)

    Cite this

    Jaworski, J. P., Bryk, P., Brower, Z., Zheng, B., Hessell, A., Rosenberg, A. F., Wu, T. T., Sanz, I., Keefer, M. C., Haigwood, N., & Kobie, J. J. (2017). Pre-existing neutralizing antibody mitigates B cell dysregulation and enhances the Envspecific antibody response in SHIV-infected rhesus macaques. PLoS One, 12(2), [e0172524]. https://doi.org/10.1371/journal.pone.0172524