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Article: Development of broad neutralization activity in simian/human immunodeficiency virus-infected rhesus macaques after long-term infection

TitleDevelopment of broad neutralization activity in simian/human immunodeficiency virus-infected rhesus macaques after long-term infection
Authors
Keywordsinfection
macaques
maturation
neutralization
simian/human immunodeficiency virus
Issue Date2018
PublisherLippincott Williams & Wilkins. The Journal's web site is located at http://www.AIDSonline.com
Citation
AIDS, 2018, v. 32 n. 5, p. 555-563 How to Cite?
AbstractObjective: Nonhuman primates (NHPs) are the only animal model that can be used to evaluate protection efficacy of HIV-1 envelope vaccines. However, whether broadly neutralizing antibodies (bnAbs) can be elicited in NHPs infected with simian/human immunodeficiency virus (SHIV) has not been fully understood. The objective of this study is to investigate whether broad neutralization activities were developed in SHIV-infected macaques after long-term infection as in humans. Design: Neutralization breadth and specificities in plasmas from SHIV-infected macaques were determined by analyzing a panel of tier 2 viruses and their mutants. Methods: Forty-four Chinese macaques infected with SHIV 1157ipd3N4, SHIV SF162P3 or SHIV CHN19P4 were followed for 54-321 weeks. Archived plasmas from 19 macaques were used to determine neutralization breadth and specificities against 17 tier 2 envelope-pseudoviruses. Results: Longitudinal plasma from three SHIV SF162P3 -infected macaques and three SHIV 1157ipd3N4 -infected macaques rarely neutralized viruses (<25%) within 1 year of infection. The neutralization breadth in two SHIV 1157ipd3N4 -infected macaques significantly increased (≥65%) by year 6. Four of six SHIV 1157ipd3N4 -infected macaques could neutralize 50-75% viruses, whereas none of macaques infected with SHIV SF162P3 or SHIV CHN19P4 could neutralize more than 25% of viruses after 6 years of infection (P = 0.035). Neutralization specificity analysis showed mutations resistant to bnAbs in V2, V3 or CD4bs regions could abrogate neutralization by year-6 plasma from three SHIV 1157ipd3N4 -infected macaques. Conclusion: These results demonstrate that bnAbs targeting common HIV-1 epitopes can be elicited in SHIV 1157ipd3N4 -infected macaques as in humans after 4-6 years of infection, and SHIV/NHP can serve as an ideal model to study bnAb maturation. © Copyright 2018 Wolters Kluwer Health, Inc. All rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/273975
ISSN
2017 Impact Factor: 4.914
2015 SCImago Journal Rankings: 3.112
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorGao, N-
dc.contributor.authorWang, W-
dc.contributor.authorGu, T-
dc.contributor.authorGuo, R-
dc.contributor.authorYu, B-
dc.contributor.authorKong, W-
dc.contributor.authorQin, C-
dc.contributor.authorGiorgi, EE-
dc.contributor.authorChen, Z-
dc.contributor.authorTownsley, S-
dc.contributor.authorHu, SL-
dc.contributor.authorYu, X-
dc.contributor.authorGao, F-
dc.date.accessioned2019-08-18T14:52:31Z-
dc.date.available2019-08-18T14:52:31Z-
dc.date.issued2018-
dc.identifier.citationAIDS, 2018, v. 32 n. 5, p. 555-563-
dc.identifier.issn0269-9370-
dc.identifier.urihttp://hdl.handle.net/10722/273975-
dc.description.abstractObjective: Nonhuman primates (NHPs) are the only animal model that can be used to evaluate protection efficacy of HIV-1 envelope vaccines. However, whether broadly neutralizing antibodies (bnAbs) can be elicited in NHPs infected with simian/human immunodeficiency virus (SHIV) has not been fully understood. The objective of this study is to investigate whether broad neutralization activities were developed in SHIV-infected macaques after long-term infection as in humans. Design: Neutralization breadth and specificities in plasmas from SHIV-infected macaques were determined by analyzing a panel of tier 2 viruses and their mutants. Methods: Forty-four Chinese macaques infected with SHIV 1157ipd3N4, SHIV SF162P3 or SHIV CHN19P4 were followed for 54-321 weeks. Archived plasmas from 19 macaques were used to determine neutralization breadth and specificities against 17 tier 2 envelope-pseudoviruses. Results: Longitudinal plasma from three SHIV SF162P3 -infected macaques and three SHIV 1157ipd3N4 -infected macaques rarely neutralized viruses (<25%) within 1 year of infection. The neutralization breadth in two SHIV 1157ipd3N4 -infected macaques significantly increased (≥65%) by year 6. Four of six SHIV 1157ipd3N4 -infected macaques could neutralize 50-75% viruses, whereas none of macaques infected with SHIV SF162P3 or SHIV CHN19P4 could neutralize more than 25% of viruses after 6 years of infection (P = 0.035). Neutralization specificity analysis showed mutations resistant to bnAbs in V2, V3 or CD4bs regions could abrogate neutralization by year-6 plasma from three SHIV 1157ipd3N4 -infected macaques. Conclusion: These results demonstrate that bnAbs targeting common HIV-1 epitopes can be elicited in SHIV 1157ipd3N4 -infected macaques as in humans after 4-6 years of infection, and SHIV/NHP can serve as an ideal model to study bnAb maturation. © Copyright 2018 Wolters Kluwer Health, Inc. All rights reserved.-
dc.languageeng-
dc.publisherLippincott Williams & Wilkins. The Journal's web site is located at http://www.AIDSonline.com-
dc.relation.ispartofAIDS-
dc.rightsThis is a non-final version of an article published in final form in (provide complete journal citation)-
dc.subjectinfection-
dc.subjectmacaques-
dc.subjectmaturation-
dc.subjectneutralization-
dc.subjectsimian/human immunodeficiency virus-
dc.titleDevelopment of broad neutralization activity in simian/human immunodeficiency virus-infected rhesus macaques after long-term infection-
dc.typeArticle-
dc.identifier.emailChen, Z: zchenai@hku.hk-
dc.identifier.authorityChen, Z=rp00243-
dc.identifier.doi10.1097/QAD.0000000000001724-
dc.identifier.pmid29239895-
dc.identifier.scopuseid_2-s2.0-85044213201-
dc.identifier.hkuros301452-
dc.identifier.volume32-
dc.identifier.issue5-
dc.identifier.spage555-
dc.identifier.epage563-
dc.identifier.isiWOS:000427975900003-
dc.publisher.placeUnited States-

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