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Development of Antibodies with Broad Neutralization Specificities against HIV-1 after Long Term SHIV Infection in Macaques

Non-human primates (NHP) are the only animal model suitable to evaluate the protection efficacy of HIV-1 vaccines. It is important to understand how and when neutralizing antibodies (nAbs) with specificities similar to those of human broadly neutralizing antibodies (bnAbs) develop in NHPs. To addres...

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Autores principales: Gao, Nan, Gai, Yanxin, Meng, Lina, Wang, Chu, Zhang, Xin, Wang, Wei, Qin, Chuan, Yu, Xianghui, Gao, Feng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7077270/
https://www.ncbi.nlm.nih.gov/pubmed/32023860
http://dx.doi.org/10.3390/v12020163
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author Gao, Nan
Gai, Yanxin
Meng, Lina
Wang, Chu
Zhang, Xin
Wang, Wei
Qin, Chuan
Yu, Xianghui
Gao, Feng
author_facet Gao, Nan
Gai, Yanxin
Meng, Lina
Wang, Chu
Zhang, Xin
Wang, Wei
Qin, Chuan
Yu, Xianghui
Gao, Feng
author_sort Gao, Nan
collection PubMed
description Non-human primates (NHP) are the only animal model suitable to evaluate the protection efficacy of HIV-1 vaccines. It is important to understand how and when neutralizing antibodies (nAbs) with specificities similar to those of human broadly neutralizing antibodies (bnAbs) develop in NHPs. To address these questions, we determined plasma neutralization specificities in two macaques which developed neutralization breadth after long-term simian/human immunodeficiency virus (SHIV) infection and identified neutralization escape mutations by analyzing the env sequences from longitudinal plasma samples. Neutralization activities targeting V2, CD4bs, V3 and gp120-gp41 interface only became detectable in week 350 plasma from macaques G1015R and G1020R using 25710 env mutants. When mapped with CAP45 env mutants, only V2 specificity was detected at week 217 and persisted until week 350 in G1015R. Neutralization escape mutations were found in CD4bs and V2 regions. However, all of them were different from those resistant mutations identified for human bnAbs. These results show that nAbs with specificities similar to human bnAbs are only detectable after long-term SHIV infection and that neutralization escape mutations in macaques are different from those found in HIV-1-infected individuals. These findings can have important implications in the best utilization of the NHP model to evaluate HIV-1 vaccines.
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spelling pubmed-70772702020-03-20 Development of Antibodies with Broad Neutralization Specificities against HIV-1 after Long Term SHIV Infection in Macaques Gao, Nan Gai, Yanxin Meng, Lina Wang, Chu Zhang, Xin Wang, Wei Qin, Chuan Yu, Xianghui Gao, Feng Viruses Article Non-human primates (NHP) are the only animal model suitable to evaluate the protection efficacy of HIV-1 vaccines. It is important to understand how and when neutralizing antibodies (nAbs) with specificities similar to those of human broadly neutralizing antibodies (bnAbs) develop in NHPs. To address these questions, we determined plasma neutralization specificities in two macaques which developed neutralization breadth after long-term simian/human immunodeficiency virus (SHIV) infection and identified neutralization escape mutations by analyzing the env sequences from longitudinal plasma samples. Neutralization activities targeting V2, CD4bs, V3 and gp120-gp41 interface only became detectable in week 350 plasma from macaques G1015R and G1020R using 25710 env mutants. When mapped with CAP45 env mutants, only V2 specificity was detected at week 217 and persisted until week 350 in G1015R. Neutralization escape mutations were found in CD4bs and V2 regions. However, all of them were different from those resistant mutations identified for human bnAbs. These results show that nAbs with specificities similar to human bnAbs are only detectable after long-term SHIV infection and that neutralization escape mutations in macaques are different from those found in HIV-1-infected individuals. These findings can have important implications in the best utilization of the NHP model to evaluate HIV-1 vaccines. MDPI 2020-01-31 /pmc/articles/PMC7077270/ /pubmed/32023860 http://dx.doi.org/10.3390/v12020163 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Gao, Nan
Gai, Yanxin
Meng, Lina
Wang, Chu
Zhang, Xin
Wang, Wei
Qin, Chuan
Yu, Xianghui
Gao, Feng
Development of Antibodies with Broad Neutralization Specificities against HIV-1 after Long Term SHIV Infection in Macaques
title Development of Antibodies with Broad Neutralization Specificities against HIV-1 after Long Term SHIV Infection in Macaques
title_full Development of Antibodies with Broad Neutralization Specificities against HIV-1 after Long Term SHIV Infection in Macaques
title_fullStr Development of Antibodies with Broad Neutralization Specificities against HIV-1 after Long Term SHIV Infection in Macaques
title_full_unstemmed Development of Antibodies with Broad Neutralization Specificities against HIV-1 after Long Term SHIV Infection in Macaques
title_short Development of Antibodies with Broad Neutralization Specificities against HIV-1 after Long Term SHIV Infection in Macaques
title_sort development of antibodies with broad neutralization specificities against hiv-1 after long term shiv infection in macaques
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7077270/
https://www.ncbi.nlm.nih.gov/pubmed/32023860
http://dx.doi.org/10.3390/v12020163
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