CD4+ T Cells Are Dispensable for Induction of Broad Heterologous HIV Neutralizing Antibodies in Rhesus Macaques

Sanghita Sarkar, David A. Spencer, Philip Barnette, Shilpi Pandey, William F. Sutton, Madhubanti Basu, Reuben E. Burch, John D. Cleveland, Alexander F. Rosenberg, Javier Rangel-Moreno, Michael C. Keefer, Ann J. Hessell, Nancy L. Haigwood, James J. Kobie

    Research output: Contribution to journalArticlepeer-review

    Abstract

    Induction of broadly neutralizing antibodies (bNAbs) is a major goal for HIV vaccine development. HIV envelope glycoprotein (Env)-specific bNAbs isolated from HIV-infected individuals exhibit substantial somatic hypermutation and correlate with T follicular helper (Tfh) responses. Using the VC10014 DNA-protein co-immunization vaccine platform consisting of gp160 plasmids and gp140 trimeric proteins derived from an HIV-1 infected subject that developed bNAbs, we determined the characteristics of the Env-specific humoral response in vaccinated rhesus macaques in the context of CD4+ T cell depletion. Unexpectedly, both CD4+ depleted and non-depleted animals developed comparable Tier 1 and 2 heterologous HIV-1 neutralizing plasma antibody titers. There was no deficit in protection from SHIV challenge, no diminution of titers of HIV Env-specific cross-clade binding antibodies, antibody dependent cellular phagocytosis, or antibody-dependent complement deposition in the CD4+ depleted animals. These collective results suggest that in the presence of diminished CD4+ T cell help, HIV neutralizing antibodies were still generated, which may have implications for developing effective HIV vaccine strategies.

    Original languageEnglish (US)
    Article number757811
    JournalFrontiers in immunology
    Volume12
    DOIs
    StatePublished - Oct 20 2021

    Keywords

    • B cell
    • CD4+ T cell
    • HIV - human immunodeficiency virus
    • antibody
    • neutralizing
    • rhesus
    • vaccine

    ASJC Scopus subject areas

    • Immunology and Allergy
    • Immunology

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