Journal
VIROLOGY
Volume 360, Issue 1, Pages 218-234Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.virol.2006.10.017
Keywords
HIV-1 genetic variation; centralized HIV-1 immunogens; HIV-1 envelope glycoprotein; subtype B
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Funding
- NCI NIH HHS [P30 CA013148, P30 CA13148] Funding Source: Medline
- NIAID NIH HHS [P01 AI 061734, U19 AI028147, N01 AI085338-002, N01AI85338, P01 AI061734, U19 AI 028147, R21 AI 055386, P30 AI27767, P30 AI027767, U19 AI067854-03, U19 AI067854, N01 AI85338, R21 AI055386, R21 AI055380] Funding Source: Medline
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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 proper-ties 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-LTNC, 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, Con13 and wild-type env immumogens induced appreciable binding, but overall only low level neutralizing antibodies. However, all four Con13 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. (c) 2006 Elsevier Inc. All rights reserved.
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