Targeted Isolation of Antibodies Directed against Major Sites of SIV Env Vulnerability.
The simian immunodeficiency virus (SIV) challenge model of lentiviral infection is often used as a model to human immunodeficiency virus type 1 (HIV-1) for studying vaccine mediated and immune correlates of protection. However, knowledge of the structure of the SIV envelope (Env) glycoprotein is lim...
Main Authors: | , , , , , , , , , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Public Library of Science (PLoS)
2016-04-01
|
Series: | PLoS Pathogens |
Online Access: | http://europepmc.org/articles/PMC4827850?pdf=render |
id |
doaj-edf0f1ad3b9441d5921afba32fbea940 |
---|---|
record_format |
Article |
spelling |
doaj-edf0f1ad3b9441d5921afba32fbea9402020-11-25T01:13:56ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742016-04-01124e100553710.1371/journal.ppat.1005537Targeted Isolation of Antibodies Directed against Major Sites of SIV Env Vulnerability.Rosemarie D MasonHugh C WellesCameron AdamsBimal K ChakrabartiJason GormanTongqing ZhouRichard NguyenSijy O'DellSabrina LusvarghiCarole A BewleyHui LiGeorge M ShawZizhang ShengLawrence ShapiroRichard WyattPeter D KwongJohn R MascolaMario RoedererThe simian immunodeficiency virus (SIV) challenge model of lentiviral infection is often used as a model to human immunodeficiency virus type 1 (HIV-1) for studying vaccine mediated and immune correlates of protection. However, knowledge of the structure of the SIV envelope (Env) glycoprotein is limited, as is knowledge of binding specificity, function and potential efficacy of SIV antibody responses. In this study we describe the use of a competitive probe binding sort strategy as well as scaffolded probes for targeted isolation of SIV Env-specific monoclonal antibodies (mAbs). We isolated nearly 70 SIV-specific mAbs directed against major sites of SIV Env vulnerability analogous to broadly neutralizing antibody (bnAb) targets of HIV-1, namely, the CD4 binding site (CD4bs), CD4-induced (CD4i)-site, peptide epitopes in variable loops 1, 2 and 3 (V1, V2, V3) and potentially glycan targets of SIV Env. The range of SIV mAbs isolated includes those exhibiting varying degrees of neutralization breadth and potency as well as others that demonstrated binding but not neutralization. Several SIV mAbs displayed broad and potent neutralization of a diverse panel of 20 SIV viral isolates with some also neutralizing HIV-2(7312A). This extensive panel of SIV mAbs will facilitate more effective use of the SIV non-human primate (NHP) model for understanding the variables in development of a HIV vaccine or immunotherapy.http://europepmc.org/articles/PMC4827850?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Rosemarie D Mason Hugh C Welles Cameron Adams Bimal K Chakrabarti Jason Gorman Tongqing Zhou Richard Nguyen Sijy O'Dell Sabrina Lusvarghi Carole A Bewley Hui Li George M Shaw Zizhang Sheng Lawrence Shapiro Richard Wyatt Peter D Kwong John R Mascola Mario Roederer |
spellingShingle |
Rosemarie D Mason Hugh C Welles Cameron Adams Bimal K Chakrabarti Jason Gorman Tongqing Zhou Richard Nguyen Sijy O'Dell Sabrina Lusvarghi Carole A Bewley Hui Li George M Shaw Zizhang Sheng Lawrence Shapiro Richard Wyatt Peter D Kwong John R Mascola Mario Roederer Targeted Isolation of Antibodies Directed against Major Sites of SIV Env Vulnerability. PLoS Pathogens |
author_facet |
Rosemarie D Mason Hugh C Welles Cameron Adams Bimal K Chakrabarti Jason Gorman Tongqing Zhou Richard Nguyen Sijy O'Dell Sabrina Lusvarghi Carole A Bewley Hui Li George M Shaw Zizhang Sheng Lawrence Shapiro Richard Wyatt Peter D Kwong John R Mascola Mario Roederer |
author_sort |
Rosemarie D Mason |
title |
Targeted Isolation of Antibodies Directed against Major Sites of SIV Env Vulnerability. |
title_short |
Targeted Isolation of Antibodies Directed against Major Sites of SIV Env Vulnerability. |
title_full |
Targeted Isolation of Antibodies Directed against Major Sites of SIV Env Vulnerability. |
title_fullStr |
Targeted Isolation of Antibodies Directed against Major Sites of SIV Env Vulnerability. |
title_full_unstemmed |
Targeted Isolation of Antibodies Directed against Major Sites of SIV Env Vulnerability. |
title_sort |
targeted isolation of antibodies directed against major sites of siv env vulnerability. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS Pathogens |
issn |
1553-7366 1553-7374 |
publishDate |
2016-04-01 |
description |
The simian immunodeficiency virus (SIV) challenge model of lentiviral infection is often used as a model to human immunodeficiency virus type 1 (HIV-1) for studying vaccine mediated and immune correlates of protection. However, knowledge of the structure of the SIV envelope (Env) glycoprotein is limited, as is knowledge of binding specificity, function and potential efficacy of SIV antibody responses. In this study we describe the use of a competitive probe binding sort strategy as well as scaffolded probes for targeted isolation of SIV Env-specific monoclonal antibodies (mAbs). We isolated nearly 70 SIV-specific mAbs directed against major sites of SIV Env vulnerability analogous to broadly neutralizing antibody (bnAb) targets of HIV-1, namely, the CD4 binding site (CD4bs), CD4-induced (CD4i)-site, peptide epitopes in variable loops 1, 2 and 3 (V1, V2, V3) and potentially glycan targets of SIV Env. The range of SIV mAbs isolated includes those exhibiting varying degrees of neutralization breadth and potency as well as others that demonstrated binding but not neutralization. Several SIV mAbs displayed broad and potent neutralization of a diverse panel of 20 SIV viral isolates with some also neutralizing HIV-2(7312A). This extensive panel of SIV mAbs will facilitate more effective use of the SIV non-human primate (NHP) model for understanding the variables in development of a HIV vaccine or immunotherapy. |
url |
http://europepmc.org/articles/PMC4827850?pdf=render |
work_keys_str_mv |
AT rosemariedmason targetedisolationofantibodiesdirectedagainstmajorsitesofsivenvvulnerability AT hughcwelles targetedisolationofantibodiesdirectedagainstmajorsitesofsivenvvulnerability AT cameronadams targetedisolationofantibodiesdirectedagainstmajorsitesofsivenvvulnerability AT bimalkchakrabarti targetedisolationofantibodiesdirectedagainstmajorsitesofsivenvvulnerability AT jasongorman targetedisolationofantibodiesdirectedagainstmajorsitesofsivenvvulnerability AT tongqingzhou targetedisolationofantibodiesdirectedagainstmajorsitesofsivenvvulnerability AT richardnguyen targetedisolationofantibodiesdirectedagainstmajorsitesofsivenvvulnerability AT sijyodell targetedisolationofantibodiesdirectedagainstmajorsitesofsivenvvulnerability AT sabrinalusvarghi targetedisolationofantibodiesdirectedagainstmajorsitesofsivenvvulnerability AT caroleabewley targetedisolationofantibodiesdirectedagainstmajorsitesofsivenvvulnerability AT huili targetedisolationofantibodiesdirectedagainstmajorsitesofsivenvvulnerability AT georgemshaw targetedisolationofantibodiesdirectedagainstmajorsitesofsivenvvulnerability AT zizhangsheng targetedisolationofantibodiesdirectedagainstmajorsitesofsivenvvulnerability AT lawrenceshapiro targetedisolationofantibodiesdirectedagainstmajorsitesofsivenvvulnerability AT richardwyatt targetedisolationofantibodiesdirectedagainstmajorsitesofsivenvvulnerability AT peterdkwong targetedisolationofantibodiesdirectedagainstmajorsitesofsivenvvulnerability AT johnrmascola targetedisolationofantibodiesdirectedagainstmajorsitesofsivenvvulnerability AT marioroederer targetedisolationofantibodiesdirectedagainstmajorsitesofsivenvvulnerability |
_version_ |
1725159872941522944 |