Increased surface expression of HIV-1 envelope is associated with improved antibody response in vaccinia prime/protein boost immunization.
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| 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.
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| Authors | Michael J Hogan, Angela Conde-Motter, Andrea P O Jordan, Lifei Yang, Brad Cleveland, Wenjin Guo, Josephine Romano, Houping Ni, Norbert Pardi, Celia C LaBranche, David C Montefiori, Shiu-Lok Hu, James A Hoxie, Drew Weissman |
| Journal | Virology (Virology) Vol. 514 Pg. 106-117 (01 15 2018) ISSN: 1096-0341 [Electronic] United States |
| PMID | 29175625 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't) |
| Copyright | Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved. |
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