Increased surface expression of HIV-1 envelope is associated with improved antibody response in vaccinia prime/protein boost immunization

Virology. 2018 Jan 15;514:106-117. doi: 10.1016/j.virol.2017.10.013. Epub 2017 Nov 22.

Abstract

HIV-1 envelope (Env)-based vaccines have so far largely failed to induce antibodies that prevent HIV-1 infection. One factor proposed to limit the immunogenicity of cell-associated Env is its low level of expression on the cell surface, restricting accessibility to antibodies. Using a vaccinia prime/protein boost protocol in mice, we explored the immunologic effects of mutations in the Env cytoplasmic tail (CT) that increased surface expression, including partial truncation and ablation of a tyrosine-dependent endocytosis motif. After vaccinia primes, CT-modified Envs induced up to 7-fold higher gp120-specific IgG, and after gp120 protein boosts, they elicited up to 16-fold greater Tier-1 HIV-1 neutralizing antibody titers, although results were variable between isolates. These data indicate that the immunogenicity of HIV-1 Env in a prime/boost vaccine can be enhanced in a strain-dependent manner by CT mutations that increase Env surface expression, thus highlighting the importance of the prime in this vaccine format.

Keywords: Antibody; Cytoplasmic tail; Envelope; HIV; Vaccine; Vaccinia.

Publication types

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

MeSH terms

  • Animals
  • Antibodies, Neutralizing / immunology
  • Antibody Formation
  • Female
  • HIV Antibodies / immunology
  • HIV Envelope Protein gp120 / administration & dosage
  • HIV Envelope Protein gp120 / genetics
  • HIV Envelope Protein gp120 / immunology*
  • HIV Infections / immunology*
  • HIV Infections / prevention & control
  • HIV Infections / virology
  • HIV-1 / genetics
  • HIV-1 / immunology*
  • Humans
  • Immunization, Secondary
  • Immunoglobulin G / immunology
  • Mice
  • Mice, Inbred C57BL
  • Vaccinia virus / immunology*

Substances

  • Antibodies, Neutralizing
  • HIV Antibodies
  • HIV Envelope Protein gp120
  • Immunoglobulin G