A directed molecular evolution approach to improved immunogenicity of the HIV-1 envelope glycoprotein.
A prophylactic vaccine is needed to slow the spread of HIV-1 infection. Optimization of the wild-type envelope glycoproteins to create immunogens that can elicit effective neutralizing antibodies is a high priority. Starting with ten genes encoding subtype B HIV-1 gp120 envelope glycoproteins and us...
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2011-01-01
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doaj-8aeb5bb4d0ea428fa8ca3ec1ac121e602020-11-25T02:13:21ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-01-0166e2092710.1371/journal.pone.0020927A directed molecular evolution approach to improved immunogenicity of the HIV-1 envelope glycoprotein.Sean X DuLi XuWenge ZhangSusan TangRebecca I BoenigHelen ChenEllaine B MarianoMichael B ZwickPaul W H I ParrenDennis R BurtonTerri WrinChristos J PetropoulosJohn A BallantyneMichael ChambersRobert G WhalenA prophylactic vaccine is needed to slow the spread of HIV-1 infection. Optimization of the wild-type envelope glycoproteins to create immunogens that can elicit effective neutralizing antibodies is a high priority. Starting with ten genes encoding subtype B HIV-1 gp120 envelope glycoproteins and using in vitro homologous DNA recombination, we created chimeric gp120 variants that were screened for their ability to bind neutralizing monoclonal antibodies. Hundreds of variants were identified with novel antigenic phenotypes that exhibit considerable sequence diversity. Immunization of rabbits with these gp120 variants demonstrated that the majority can induce neutralizing antibodies to HIV-1. One novel variant, called ST-008, induced significantly improved neutralizing antibody responses when assayed against a large panel of primary HIV-1 isolates. Further study of various deletion constructs of ST-008 showed that the enhanced immunogenicity results from a combination of effective DNA priming, an enhanced V3-based response, and an improved response to the constant backbone sequences.http://europepmc.org/articles/PMC3126809?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Sean X Du Li Xu Wenge Zhang Susan Tang Rebecca I Boenig Helen Chen Ellaine B Mariano Michael B Zwick Paul W H I Parren Dennis R Burton Terri Wrin Christos J Petropoulos John A Ballantyne Michael Chambers Robert G Whalen |
spellingShingle |
Sean X Du Li Xu Wenge Zhang Susan Tang Rebecca I Boenig Helen Chen Ellaine B Mariano Michael B Zwick Paul W H I Parren Dennis R Burton Terri Wrin Christos J Petropoulos John A Ballantyne Michael Chambers Robert G Whalen A directed molecular evolution approach to improved immunogenicity of the HIV-1 envelope glycoprotein. PLoS ONE |
author_facet |
Sean X Du Li Xu Wenge Zhang Susan Tang Rebecca I Boenig Helen Chen Ellaine B Mariano Michael B Zwick Paul W H I Parren Dennis R Burton Terri Wrin Christos J Petropoulos John A Ballantyne Michael Chambers Robert G Whalen |
author_sort |
Sean X Du |
title |
A directed molecular evolution approach to improved immunogenicity of the HIV-1 envelope glycoprotein. |
title_short |
A directed molecular evolution approach to improved immunogenicity of the HIV-1 envelope glycoprotein. |
title_full |
A directed molecular evolution approach to improved immunogenicity of the HIV-1 envelope glycoprotein. |
title_fullStr |
A directed molecular evolution approach to improved immunogenicity of the HIV-1 envelope glycoprotein. |
title_full_unstemmed |
A directed molecular evolution approach to improved immunogenicity of the HIV-1 envelope glycoprotein. |
title_sort |
directed molecular evolution approach to improved immunogenicity of the hiv-1 envelope glycoprotein. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2011-01-01 |
description |
A prophylactic vaccine is needed to slow the spread of HIV-1 infection. Optimization of the wild-type envelope glycoproteins to create immunogens that can elicit effective neutralizing antibodies is a high priority. Starting with ten genes encoding subtype B HIV-1 gp120 envelope glycoproteins and using in vitro homologous DNA recombination, we created chimeric gp120 variants that were screened for their ability to bind neutralizing monoclonal antibodies. Hundreds of variants were identified with novel antigenic phenotypes that exhibit considerable sequence diversity. Immunization of rabbits with these gp120 variants demonstrated that the majority can induce neutralizing antibodies to HIV-1. One novel variant, called ST-008, induced significantly improved neutralizing antibody responses when assayed against a large panel of primary HIV-1 isolates. Further study of various deletion constructs of ST-008 showed that the enhanced immunogenicity results from a combination of effective DNA priming, an enhanced V3-based response, and an improved response to the constant backbone sequences. |
url |
http://europepmc.org/articles/PMC3126809?pdf=render |
work_keys_str_mv |
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