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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Hogan, MJ; Conde-Motter, A; Jordan, APO; Yang, L; Cleveland, B; Guo, W; Romano, J; Ni, H; Pardi, N; LaBranche, CC; Montefiori, DC; Hu, S-L; Hoxie, JA; Weissman, D

Published Date

  • January 2018

Published In

Volume / Issue

  • 514 /

Start / End Page

  • 106 - 117

PubMed ID

  • 29175625

Pubmed Central ID

  • 29175625

Electronic International Standard Serial Number (EISSN)

  • 2514-4138

International Standard Serial Number (ISSN)

  • 1096-0341

Digital Object Identifier (DOI)

  • 10.1016/j.virol.2017.10.013

Language

  • eng