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

    Research output: Contribution to journalArticle

    1 Citation (Scopus)

    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

    Fingerprint

    Macaca mulatta
    Neutralizing Antibodies
    neutralizing antibodies
    B-lymphocytes
    Antibody Formation
    B-Lymphocytes
    Cells
    antibodies
    Antibodies
    Animals
    animals
    sterilizing
    Infection
    infection
    immunoglobulins
    Immunoglobulins
    Plasmas
    Immunoglobulin D
    AIDS Vaccines
    Viremia

    ASJC Scopus subject areas

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

    Cite this

    Pre-existing neutralizing antibody mitigates B cell dysregulation and enhances the Envspecific antibody response in SHIV-infected rhesus macaques. / Jaworski, Juan Pablo; Bryk, Peter; Brower, Zachary; Zheng, Bo; Hessell, Ann; Rosenberg, Alexander F.; Wu, Tong Tong; Sanz, Ignacio; Keefer, Michael C.; Haigwood, Nancy; Kobie, James J.

    In: PLoS One, Vol. 12, No. 2, e0172524, 01.02.2017.

    Research output: Contribution to journalArticle

    Jaworski, Juan Pablo ; Bryk, Peter ; Brower, Zachary ; Zheng, Bo ; Hessell, Ann ; Rosenberg, Alexander F. ; Wu, Tong Tong ; Sanz, Ignacio ; Keefer, Michael C. ; Haigwood, Nancy ; Kobie, James J. / Pre-existing neutralizing antibody mitigates B cell dysregulation and enhances the Envspecific antibody response in SHIV-infected rhesus macaques. In: PLoS One. 2017 ; Vol. 12, No. 2.
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    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.",
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    AU - Hessell, Ann

    AU - Rosenberg, Alexander F.

    AU - Wu, Tong Tong

    AU - Sanz, Ignacio

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    AU - Kobie, James J.

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