Antigenicity and immunogenicity of HIV-1 consensus subtype B envelope glycoproteins

Virology. 2007 Mar 30;360(1):218-34. doi: 10.1016/j.virol.2006.10.017. Epub 2006 Nov 13.

Abstract

"Centralized" (ancestral and consensus) HIV-1 envelope immunogens induce broadly cross-reactive T cell responses in laboratory animals; however, their potential to elicit cross-reactive neutralizing antibodies has not been fully explored. Here, we report the construction of a panel of consensus subtype B (ConB) envelopes and compare their biologic, antigenic, and immunogenic properties to those of two wild-type Env controls from individuals with early and acute HIV-1 infection. Glycoprotein expressed from full-length (gp160), uncleaved (gp160-UNC), truncated (gp145), and N-linked glycosylation site deleted (gp160-201N/S) versions of the ConB env gene were packaged into virions and, except for the fusion defective gp160-UNC, mediated infection via the CCR5 co-receptor. Pseudovirions containing ConB Envs were sensitive to neutralization by patient plasma and monoclonal antibodies, indicating the preservation of neutralizing epitopes found in contemporary subtype B viruses. When used as DNA vaccines in guinea pigs, ConB and wild-type env immunogens induced appreciable binding, but overall only low level neutralizing antibodies. However, all four ConB immunogens were significantly more potent than one wild-type vaccine at eliciting neutralizing antibodies against a panel of tier 1 and tier 2 viruses, and ConB gp145 and gp160 were significantly more potent than both wild-type vaccines at inducing neutralizing antibodies against tier 1 viruses. Thus, consensus subtype B env immunogens appear to be at least as good as, and in some instances better than, wild-type B env immunogens at inducing a neutralizing antibody response, and are amenable to further improvement by specific gene modifications.

Publication types

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

MeSH terms

  • AIDS Vaccines / administration & dosage
  • Amino Acid Sequence
  • Animals
  • Antibody Specificity
  • Female
  • Genes, env / genetics
  • Genetic Variation
  • Glycoproteins / genetics
  • Glycoproteins / immunology
  • Guinea Pigs
  • HIV Antibodies / blood
  • HIV Antibodies / immunology
  • HIV Antigens / immunology
  • HIV Envelope Protein gp160 / immunology
  • HIV Infections / blood
  • HIV Infections / immunology*
  • HIV-1 / classification
  • HIV-1 / immunology*
  • Humans
  • Immune Sera / immunology
  • Immunization*
  • Injections, Intramuscular
  • Molecular Sequence Data
  • Neutralization Tests
  • Sequence Alignment
  • Species Specificity
  • Vaccines, DNA / administration & dosage
  • Viral Envelope Proteins / genetics
  • Viral Envelope Proteins / immunology*

Substances

  • AIDS Vaccines
  • Glycoproteins
  • HIV Antibodies
  • HIV Antigens
  • HIV Envelope Protein gp160
  • Immune Sera
  • Vaccines, DNA
  • Viral Envelope Proteins