Murine antibody responses to cleaved soluble HIV-1 envelope trimers are highly restricted in specificity Academic Article uri icon

Overview

MeSH Major

  • Antibodies, Neutralizing
  • Antigens, Viral
  • HIV Antibodies
  • HIV Infections
  • Immunoglobulin G
  • env Gene Products, Human Immunodeficiency Virus

abstract

  • Human HIV vaccine efficacy trials have not generated meaningful neutralizing antibodies to circulating HIV strains. One possible hindrance has been the lack of immunogens that properly mimic the native conformation of the HIV envelope trimer protein. Here, we tested the first generation of soluble, native-like envelope trimer immunogens in a conventional mouse model. We attempted to generate neutralizing antibodies to neutralization-resistant circulating HIV strains. Various vaccine strategies failed to induce neutralizing antibodies to a neutralization-resistant HIV strain. Further analysis revealed that mouse antibodies targeted areas near the bottom of the soluble envelope trimers. These areas are not easily accessible on the HIV virion due to occlusion by the viral membrane and may have resulted from an absence of glycan shielding. Our results suggest that obscuring the bottom of soluble envelope trimers is a useful strategy to reduce antibody responses to epitopes that are not useful for virus neutralization.

publication date

  • January 2015

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC4580201

Digital Object Identifier (DOI)

  • 10.1128/JVI.01653-15

PubMed ID

  • 26246566

Additional Document Info

start page

  • 10383

end page

  • 98

volume

  • 89

number

  • 20