skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

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

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 1more » 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.« less

Authors:
; ; ; ; ; ; ; ;  [1]; ;  [2]; ;  [3];  [4];  [5];  [6];  [7]
  1. Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294 (United States)
  2. Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294 (United States)
  3. Duke Human Vaccine Institute, Duke University Medical Center, Durham, NC 27710 (United States)
  4. Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294 (United States)|[Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294 (United States)|[Howard Hughes Medical Institute, University of Alabama at Birmingham, Birmingham, AL 35294 (United States)
  5. Department of Mathematics, University of Manchester Institute of Technology, Manchester M601QD (United Kingdom)
  6. Los Alamos National Laboratory, Los Alamos, NM 87545 (United States)|[Santa Fe Institute, Santa Fe, NM 87501 (United States)
  7. Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294 (United States)|[Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294 (United States). E-mail: bhahn@uab.edu
Publication Date:
OSTI Identifier:
20977006
Resource Type:
Journal Article
Resource Relation:
Journal Name: Virology; Journal Volume: 360; Journal Issue: 1; Other Information: DOI: 10.1016/j.virol.2006.10.017; PII: S0042-6822(06)00748-3; Copyright (c) 2006 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; AIDS VIRUS; DNA; GENES; GLYCOPROTEINS; GUINEA PIGS; LABORATORY ANIMALS; MONOCLONAL ANTIBODIES; PATIENTS; RECEPTORS; VACCINES

Citation Formats

Kothe, Denise L., Decker, Julie M., Li Yingying, Weng Zhiping, Bibollet-Ruche, Frederic, Zammit, Kenneth P., Salazar, Maria G., Chen, Yalu, Salazar-Gonzalez, Jesus F., Moldoveanu, Zina, Mestecky, Jiri, Gao Feng, Haynes, Barton F., Shaw, George M., Muldoon, Mark, Korber, Bette T.M., and Hahn, Beatrice H.. Antigenicity and immunogenicity of HIV-1 consensus subtype B envelope glycoproteins. United States: N. p., 2007. Web. doi:10.1016/j.virol.2006.10.017.
Kothe, Denise L., Decker, Julie M., Li Yingying, Weng Zhiping, Bibollet-Ruche, Frederic, Zammit, Kenneth P., Salazar, Maria G., Chen, Yalu, Salazar-Gonzalez, Jesus F., Moldoveanu, Zina, Mestecky, Jiri, Gao Feng, Haynes, Barton F., Shaw, George M., Muldoon, Mark, Korber, Bette T.M., & Hahn, Beatrice H.. Antigenicity and immunogenicity of HIV-1 consensus subtype B envelope glycoproteins. United States. doi:10.1016/j.virol.2006.10.017.
Kothe, Denise L., Decker, Julie M., Li Yingying, Weng Zhiping, Bibollet-Ruche, Frederic, Zammit, Kenneth P., Salazar, Maria G., Chen, Yalu, Salazar-Gonzalez, Jesus F., Moldoveanu, Zina, Mestecky, Jiri, Gao Feng, Haynes, Barton F., Shaw, George M., Muldoon, Mark, Korber, Bette T.M., and Hahn, Beatrice H.. Fri . "Antigenicity and immunogenicity of HIV-1 consensus subtype B envelope glycoproteins". United States. doi:10.1016/j.virol.2006.10.017.
@article{osti_20977006,
title = {Antigenicity and immunogenicity of HIV-1 consensus subtype B envelope glycoproteins},
author = {Kothe, Denise L. and Decker, Julie M. and Li Yingying and Weng Zhiping and Bibollet-Ruche, Frederic and Zammit, Kenneth P. and Salazar, Maria G. and Chen, Yalu and Salazar-Gonzalez, Jesus F. and Moldoveanu, Zina and Mestecky, Jiri and Gao Feng and Haynes, Barton F. and Shaw, George M. and Muldoon, Mark and Korber, Bette T.M. and Hahn, Beatrice H.},
abstractNote = {'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.},
doi = {10.1016/j.virol.2006.10.017},
journal = {Virology},
number = 1,
volume = 360,
place = {United States},
year = {Fri Mar 30 00:00:00 EDT 2007},
month = {Fri Mar 30 00:00:00 EDT 2007}
}