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Extensive dissemination and intraclonal maturation of HIV Env vaccine-induced B cell responses

Well-ordered HIV-1 envelope glycoprotein (Env) trimers are prioritized for clinical evaluation, and there is a need for an improved understanding about how elicited B cell responses evolve following immunization. To accomplish this, we prime-boosted rhesus macaques with clade C NFL trimers and ident...

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Autores principales: Phad, Ganesh E., Pushparaj, Pradeepa, Tran, Karen, Dubrovskaya, Viktoriya, Àdori, Monika, Martinez-Murillo, Paola, Vázquez Bernat, Néstor, Singh, Suruchi, Dionne, Gilman, O’Dell, Sijy, Bhullar, Komal, Narang, Sanjana, Sorini, Chiara, Villablanca, Eduardo J., Sundling, Christopher, Murrell, Benjamin, Mascola, John R., Shapiro, Lawrence, Pancera, Marie, Martin, Marcel, Corcoran, Martin, Wyatt, Richard T., Karlsson Hedestam, Gunilla B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Rockefeller University Press 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7041718/
https://www.ncbi.nlm.nih.gov/pubmed/31704807
http://dx.doi.org/10.1084/jem.20191155
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author Phad, Ganesh E.
Pushparaj, Pradeepa
Tran, Karen
Dubrovskaya, Viktoriya
Àdori, Monika
Martinez-Murillo, Paola
Vázquez Bernat, Néstor
Singh, Suruchi
Dionne, Gilman
O’Dell, Sijy
Bhullar, Komal
Narang, Sanjana
Sorini, Chiara
Villablanca, Eduardo J.
Sundling, Christopher
Murrell, Benjamin
Mascola, John R.
Shapiro, Lawrence
Pancera, Marie
Martin, Marcel
Corcoran, Martin
Wyatt, Richard T.
Karlsson Hedestam, Gunilla B.
author_facet Phad, Ganesh E.
Pushparaj, Pradeepa
Tran, Karen
Dubrovskaya, Viktoriya
Àdori, Monika
Martinez-Murillo, Paola
Vázquez Bernat, Néstor
Singh, Suruchi
Dionne, Gilman
O’Dell, Sijy
Bhullar, Komal
Narang, Sanjana
Sorini, Chiara
Villablanca, Eduardo J.
Sundling, Christopher
Murrell, Benjamin
Mascola, John R.
Shapiro, Lawrence
Pancera, Marie
Martin, Marcel
Corcoran, Martin
Wyatt, Richard T.
Karlsson Hedestam, Gunilla B.
author_sort Phad, Ganesh E.
collection PubMed
description Well-ordered HIV-1 envelope glycoprotein (Env) trimers are prioritized for clinical evaluation, and there is a need for an improved understanding about how elicited B cell responses evolve following immunization. To accomplish this, we prime-boosted rhesus macaques with clade C NFL trimers and identified 180 unique Ab lineages from ∼1,000 single-sorted Env-specific memory B cells. We traced all lineages in high-throughput heavy chain (HC) repertoire (Rep-seq) data generated from multiple immune compartments and time points and expressed several as monoclonal Abs (mAbs). Our results revealed broad dissemination and high levels of somatic hypermutation (SHM) of most lineages, including tier 2 virus neutralizing lineages, following boosting. SHM was highest in the Ab complementarity determining regions (CDRs) but also surprisingly high in the framework regions (FRs), especially FR3. Our results demonstrate the capacity of the immune system to affinity-mature large numbers of Env-specific B cell lineages simultaneously, supporting the use of regimens consisting of repeated boosts to improve each Ab, even those belonging to less expanded lineages.
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spelling pubmed-70417182020-08-03 Extensive dissemination and intraclonal maturation of HIV Env vaccine-induced B cell responses Phad, Ganesh E. Pushparaj, Pradeepa Tran, Karen Dubrovskaya, Viktoriya Àdori, Monika Martinez-Murillo, Paola Vázquez Bernat, Néstor Singh, Suruchi Dionne, Gilman O’Dell, Sijy Bhullar, Komal Narang, Sanjana Sorini, Chiara Villablanca, Eduardo J. Sundling, Christopher Murrell, Benjamin Mascola, John R. Shapiro, Lawrence Pancera, Marie Martin, Marcel Corcoran, Martin Wyatt, Richard T. Karlsson Hedestam, Gunilla B. J Exp Med Research Articles Well-ordered HIV-1 envelope glycoprotein (Env) trimers are prioritized for clinical evaluation, and there is a need for an improved understanding about how elicited B cell responses evolve following immunization. To accomplish this, we prime-boosted rhesus macaques with clade C NFL trimers and identified 180 unique Ab lineages from ∼1,000 single-sorted Env-specific memory B cells. We traced all lineages in high-throughput heavy chain (HC) repertoire (Rep-seq) data generated from multiple immune compartments and time points and expressed several as monoclonal Abs (mAbs). Our results revealed broad dissemination and high levels of somatic hypermutation (SHM) of most lineages, including tier 2 virus neutralizing lineages, following boosting. SHM was highest in the Ab complementarity determining regions (CDRs) but also surprisingly high in the framework regions (FRs), especially FR3. Our results demonstrate the capacity of the immune system to affinity-mature large numbers of Env-specific B cell lineages simultaneously, supporting the use of regimens consisting of repeated boosts to improve each Ab, even those belonging to less expanded lineages. Rockefeller University Press 2019-11-08 /pmc/articles/PMC7041718/ /pubmed/31704807 http://dx.doi.org/10.1084/jem.20191155 Text en © 2019 Phad et al. http://www.rupress.org/terms/https://creativecommons.org/licenses/by-nc-sa/4.0/This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Research Articles
Phad, Ganesh E.
Pushparaj, Pradeepa
Tran, Karen
Dubrovskaya, Viktoriya
Àdori, Monika
Martinez-Murillo, Paola
Vázquez Bernat, Néstor
Singh, Suruchi
Dionne, Gilman
O’Dell, Sijy
Bhullar, Komal
Narang, Sanjana
Sorini, Chiara
Villablanca, Eduardo J.
Sundling, Christopher
Murrell, Benjamin
Mascola, John R.
Shapiro, Lawrence
Pancera, Marie
Martin, Marcel
Corcoran, Martin
Wyatt, Richard T.
Karlsson Hedestam, Gunilla B.
Extensive dissemination and intraclonal maturation of HIV Env vaccine-induced B cell responses
title Extensive dissemination and intraclonal maturation of HIV Env vaccine-induced B cell responses
title_full Extensive dissemination and intraclonal maturation of HIV Env vaccine-induced B cell responses
title_fullStr Extensive dissemination and intraclonal maturation of HIV Env vaccine-induced B cell responses
title_full_unstemmed Extensive dissemination and intraclonal maturation of HIV Env vaccine-induced B cell responses
title_short Extensive dissemination and intraclonal maturation of HIV Env vaccine-induced B cell responses
title_sort extensive dissemination and intraclonal maturation of hiv env vaccine-induced b cell responses
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7041718/
https://www.ncbi.nlm.nih.gov/pubmed/31704807
http://dx.doi.org/10.1084/jem.20191155
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