HIV vaccine delayed boosting increases Env variable region 2-specific antibody effector functions

JCI Insight. 2020 Jan 30;5(2):e131437. doi: 10.1172/jci.insight.131437.

Abstract

In the RV144 HIV-1 phase III trial, vaccine efficacy directly correlated with the magnitude of the variable region 2-specific (V2-specific) IgG antibody response, and in the presence of low plasma IgA levels, with the magnitude of plasma antibody-dependent cellular cytotoxicity. Reenrollment of RV144 vaccinees in the RV305 trial offered the opportunity to define the function, maturation, and persistence of vaccine-induced V2-specific and other mAb responses after boosting. We show that the RV144 vaccine regimen induced persistent V2 and other HIV-1 envelope-specific memory B cell clonal lineages that could be identified throughout the approximately 11-year vaccination period. Subsequent boosts increased somatic hypermutation, a critical requirement for antibody affinity maturation. Characterization of 22 vaccine-induced V2-specific mAbs with epitope specificities distinct from previously characterized RV144 V2-specific mAbs CH58 and CH59 found increased in vitro antibody-mediated effector functions. Thus, when inducing non-neutralizing antibodies, one method by which to improve HIV-1 vaccine efficacy may be through late boosting to diversify the V2-specific response to increase the breadth of antibody-mediated anti-HIV-1 effector functions.

Keywords: AIDS vaccine; AIDS/HIV.

MeSH terms

  • AIDS Vaccines / chemistry
  • AIDS Vaccines / immunology*
  • Antibodies, Monoclonal / chemistry
  • Antibodies, Monoclonal / genetics
  • Antibodies, Monoclonal / immunology
  • Antibody-Dependent Cell Cytotoxicity
  • Clinical Trials as Topic
  • Epitopes / genetics
  • Epitopes / immunology
  • HIV Antibodies / chemistry
  • HIV Antibodies / genetics
  • HIV Antibodies / immunology*
  • HIV Infections / immunology
  • HIV Infections / prevention & control
  • HIV-1 / immunology
  • Humans
  • Immunization, Secondary
  • Immunoglobulin Variable Region / genetics*
  • Immunoglobulin Variable Region / immunology*
  • Models, Molecular
  • Mutation
  • Protein Conformation
  • Viral Vaccines
  • X-Ray Diffraction
  • env Gene Products, Human Immunodeficiency Virus / genetics
  • env Gene Products, Human Immunodeficiency Virus / immunology

Substances

  • AIDS Vaccines
  • AIDSVAX
  • ALVAC vaccine
  • Antibodies, Monoclonal
  • Epitopes
  • HIV Antibodies
  • Immunoglobulin Variable Region
  • Viral Vaccines
  • env Gene Products, Human Immunodeficiency Virus