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Anti-Drug Antibodies in Pigtailed Macaques Receiving HIV Broadly Neutralising Antibody PGT121

Broadly neutralising antibodies (bNAbs) may play an important role in future strategies for HIV control. The development of anti-drug antibody (ADA) responses can reduce the efficacy of passively transferred bNAbs but the impact of ADA is imperfectly understood. We previously showed that therapeutic...

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Autores principales: Lee, Wen Shi, Reynaldi, Arnold, Amarasena, Thakshila, Davenport, Miles P., Parsons, Matthew S., Kent, Stephen J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8636046/
https://www.ncbi.nlm.nih.gov/pubmed/34867979
http://dx.doi.org/10.3389/fimmu.2021.749891
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author Lee, Wen Shi
Reynaldi, Arnold
Amarasena, Thakshila
Davenport, Miles P.
Parsons, Matthew S.
Kent, Stephen J.
author_facet Lee, Wen Shi
Reynaldi, Arnold
Amarasena, Thakshila
Davenport, Miles P.
Parsons, Matthew S.
Kent, Stephen J.
author_sort Lee, Wen Shi
collection PubMed
description Broadly neutralising antibodies (bNAbs) may play an important role in future strategies for HIV control. The development of anti-drug antibody (ADA) responses can reduce the efficacy of passively transferred bNAbs but the impact of ADA is imperfectly understood. We previously showed that therapeutic administration of the anti-HIV bNAb PGT121 (either WT or LALA version) controlled viraemia in pigtailed macaques with ongoing SHIV infection. We now report on 23 macaques that had multiple treatments with PGT121. We found that an increasing number of intravenous doses of PGT121 or human IgG1 isotype control antibodies (2-4 doses) results in anti-PGT121 ADA induction and low plasma concentrations of PGT121. ADA was associated with poor or absent suppression of SHIV viremia. Notably, ADA within macaque plasma recognised another human bNAb 10E8 but did not bind to the variable domains of PGT121, suggesting that ADA were primarily directed against the constant regions of the human antibodies. These findings have implications for the development of preclinical studies examining multiple infusions of human bNAbs.
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spelling pubmed-86360462021-12-02 Anti-Drug Antibodies in Pigtailed Macaques Receiving HIV Broadly Neutralising Antibody PGT121 Lee, Wen Shi Reynaldi, Arnold Amarasena, Thakshila Davenport, Miles P. Parsons, Matthew S. Kent, Stephen J. Front Immunol Immunology Broadly neutralising antibodies (bNAbs) may play an important role in future strategies for HIV control. The development of anti-drug antibody (ADA) responses can reduce the efficacy of passively transferred bNAbs but the impact of ADA is imperfectly understood. We previously showed that therapeutic administration of the anti-HIV bNAb PGT121 (either WT or LALA version) controlled viraemia in pigtailed macaques with ongoing SHIV infection. We now report on 23 macaques that had multiple treatments with PGT121. We found that an increasing number of intravenous doses of PGT121 or human IgG1 isotype control antibodies (2-4 doses) results in anti-PGT121 ADA induction and low plasma concentrations of PGT121. ADA was associated with poor or absent suppression of SHIV viremia. Notably, ADA within macaque plasma recognised another human bNAb 10E8 but did not bind to the variable domains of PGT121, suggesting that ADA were primarily directed against the constant regions of the human antibodies. These findings have implications for the development of preclinical studies examining multiple infusions of human bNAbs. Frontiers Media S.A. 2021-11-11 /pmc/articles/PMC8636046/ /pubmed/34867979 http://dx.doi.org/10.3389/fimmu.2021.749891 Text en Copyright © 2021 Lee, Reynaldi, Amarasena, Davenport, Parsons and Kent https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Lee, Wen Shi
Reynaldi, Arnold
Amarasena, Thakshila
Davenport, Miles P.
Parsons, Matthew S.
Kent, Stephen J.
Anti-Drug Antibodies in Pigtailed Macaques Receiving HIV Broadly Neutralising Antibody PGT121
title Anti-Drug Antibodies in Pigtailed Macaques Receiving HIV Broadly Neutralising Antibody PGT121
title_full Anti-Drug Antibodies in Pigtailed Macaques Receiving HIV Broadly Neutralising Antibody PGT121
title_fullStr Anti-Drug Antibodies in Pigtailed Macaques Receiving HIV Broadly Neutralising Antibody PGT121
title_full_unstemmed Anti-Drug Antibodies in Pigtailed Macaques Receiving HIV Broadly Neutralising Antibody PGT121
title_short Anti-Drug Antibodies in Pigtailed Macaques Receiving HIV Broadly Neutralising Antibody PGT121
title_sort anti-drug antibodies in pigtailed macaques receiving hiv broadly neutralising antibody pgt121
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8636046/
https://www.ncbi.nlm.nih.gov/pubmed/34867979
http://dx.doi.org/10.3389/fimmu.2021.749891
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