Enhancing and shaping the immunogenicity of native-like HIV-1 envelope trimers with a two-component protein nanoparticle Academic Article uri icon

Overview

MeSH Major

  • AIDS Vaccines
  • Antibodies, Neutralizing
  • Epitopes
  • HIV Antibodies
  • HIV-1
  • env Gene Products, Human Immunodeficiency Virus

abstract

  • The development of native-like HIV-1 envelope (Env) trimer antigens has enabled the induction of neutralizing antibody (NAb) responses against neutralization-resistant HIV-1 strains in animal models. However, NAb responses are relatively weak and narrow in specificity. Displaying antigens in a multivalent fashion on nanoparticles (NPs) is an established strategy to increase their immunogenicity. Here we present the design and characterization of two-component protein NPs displaying 20 stabilized SOSIP trimers from various HIV-1 strains. The two-component nature permits the incorporation of exclusively well-folded, native-like Env trimers into NPs that self-assemble in vitro with high efficiency. Immunization studies show that the NPs are particularly efficacious as priming immunogens, improve the quality of the Ab response over a conventional one-component nanoparticle system, and are most effective when SOSIP trimers with an apex-proximate neutralizing epitope are displayed. Their ability to enhance and shape the immunogenicity of SOSIP trimers make these NPs a promising immunogen platform.

authors

publication date

  • September 19, 2019

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC6753213

Digital Object Identifier (DOI)

  • 10.1038/s41467-019-12080-1

PubMed ID

  • 31537780

Additional Document Info

start page

  • 4272

volume

  • 10

number

  • 1