Vaccine-elicited SIV and HIV Envelope-Specific IgA and IgG Memory B Cells in Rhesus Macaque Peripheral Blood Correlate With Functional Antibody Responses and Reduced Viremia

Vaccine. 2011 Apr 12;29(17):3310-9. doi: 10.1016/j.vaccine.2011.02.066. Epub 2011 Mar 5.

Abstract

An effective HIV vaccine requires strong systemic and mucosal, cellular and humoral immunity. Numerous non-human primate studies have investigated memory T cells, but not memory B cells. Humoral immunologic memory is mediated by long-lived antibody-secreting plasma cells and differentiation of memory B cells into short-lived plasma blasts following re-exposure to immunizing antigen. Here we studied memory B cells in vaccinated rhesus macaques. PBMC were stimulated polyclonally using CD40 Ligand, IL-21 and CpG to induce B cell proliferation and differentiation into antibody secreting cells (ASCs). Flow cytometry was used for phenotyping and evaluating proliferation by CFSE dilution. B cell responses were quantified by ELISPOT. Methodology was established using PBMC of vaccinated elite-controller macaques that exhibited strong, multi-functional antibody activities. Subsequently, memory B cells elicited by two replicating Ad-recombinant prime/envelope boost regimens were retrospectively evaluated pre- and post-SIV and SHIV challenges. The vaccine regimens induced SIV and HIV Env-specific IgG and IgA memory B cells. Prior to challenge, IgA memory B cells were more numerous than IgG memory B cells, reflecting the mucosal priming immunizations. Pre- and post-challenge memory B cells were correlated with functional antibody responses including antibody-dependent cellular cytotoxicity (ADCC), antibody-dependent cell-mediated viral inhibition (ADCVI) and transcytosis inhibition. Post-challenge, Env-specific IgG and IgA memory B cells were correlated with reduced chronic viremia. We conclude that functional antibody responses elicited by our prime/boost regimen were effectively incorporated into the memory B cell pool where they contributed to control of viremia following re-exposure to the immunizing antigen.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • B-Lymphocytes / immunology*
  • Enzyme-Linked Immunospot Assay
  • Flow Cytometry
  • HIV / immunology*
  • Immunoglobulin A / blood*
  • Immunoglobulin G / blood*
  • Immunologic Memory
  • Macaca mulatta
  • Simian Immunodeficiency Virus / immunology*
  • Viral Envelope Proteins / immunology*
  • Viremia / prevention & control*

Substances

  • Immunoglobulin A
  • Immunoglobulin G
  • Viral Envelope Proteins