Impact of vaccine type on HIV-1 vaccine elicited antibody durability and B cell gene signature

Sci Rep. 2020 Aug 3;10(1):13031. doi: 10.1038/s41598-020-69007-w.

Abstract

Efficacious HIV-1 vaccination requires elicitation of long-lived antibody responses. However, our understanding of how different vaccine types elicit durable antibody responses is lacking. To assess the impact of vaccine type on antibody responses, we measured IgG isotypes against four consensus HIV antigens from 2 weeks to 10 years post HIV-1 vaccination and used mixed effects models to estimate half-life of responses in four human clinical trials. Compared to protein-boosted regimens, half-lives of gp120-specific antibodies were longer but peak magnitudes were lower in Modified Vaccinia Ankara (MVA)-boosted regimens. Furthermore, gp120-specific B cell transcriptomics from MVA-boosted and protein-boosted vaccines revealed a distinct signature at a peak (2 weeks after last vaccination) including CD19, CD40, and FCRL2-5 activation along with increased B cell receptor signaling. Additional analysis revealed contributions of RIG-I-like receptor pathway and genes such as SMAD5 and IL-32 to antibody durability. Thus, this study provides novel insights into vaccine induced antibody durability and B-cell receptor signaling.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • AIDS Vaccines / immunology*
  • Antibody Formation / immunology
  • B-Lymphocytes / immunology*
  • Clinical Trials as Topic
  • Gene Expression Profiling*
  • Gene Expression Regulation
  • HIV Antibodies / immunology*
  • HIV Infections / genetics*
  • HIV Infections / immunology*
  • HIV-1 / immunology*
  • Half-Life
  • Humans
  • Immunization, Secondary
  • Linear Models
  • Lymphocyte Activation / immunology
  • Receptors, Antigen, B-Cell / metabolism
  • Signal Transduction
  • Vaccination
  • Vaccinia virus / immunology

Substances

  • AIDS Vaccines
  • HIV Antibodies
  • Receptors, Antigen, B-Cell