Elicitation of Robust Tier 2 Neutralizing Antibody Responses in Nonhuman Primates by HIV Envelope Trimer Immunization Using Optimized Approaches. Academic Article uri icon

Overview

abstract

  • The development of stabilized recombinant HIV envelope trimers that mimic the virion surface molecule has increased enthusiasm for a neutralizing antibody (nAb)-based HIV vaccine. However, there is limited experience with recombinant trimers as immunogens in nonhuman primates, which are typically used as a model for humans. Here, we tested multiple immunogens and immunization strategies head-to-head to determine their impact on the quantity, quality, and kinetics of autologous tier 2 nAb development. A bilateral, adjuvanted, subcutaneous immunization protocol induced reproducible tier 2 nAb responses after only two immunizations 8 weeks apart, and these were further enhanced by a third immunization with BG505 SOSIP trimer. We identified immunogens that minimized non-neutralizing V3 responses and demonstrated that continuous immunogen delivery could enhance nAb responses. nAb responses were strongly associated with germinal center reactions, as assessed by lymph node fine needle aspiration. This study provides a framework for preclinical and clinical vaccine studies targeting nAb elicitation.

authors

publication date

  • June 20, 2017

Research

keywords

  • AIDS Vaccines
  • Antibodies, Neutralizing
  • Germinal Center
  • HIV Antibodies
  • HIV Infections
  • HIV-1

Identity

PubMed Central ID

  • PMC5483234

Scopus Document Identifier

  • 85025101545

Digital Object Identifier (DOI)

  • 10.1016/j.immuni.2017.05.007

PubMed ID

  • 28636956

Additional Document Info

volume

  • 46

issue

  • 6