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:	Wen Shi Lee, Arnold Reynaldi, Thakshila Amarasena, Miles P. Davenport, Matthew S. Parsons, Stephen J. Kent
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	HIV broadly neutralizing antibodies (bNAb) PGT121 anti-drug antibodies (ADA) pigtailed macaque Immunologic diseases. Allergy RC581-607
Acceso en línea:	https://doaj.org/article/099d8252a5c742e2aa9272fa91e71d68
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spelling	oai:doaj.org-article:099d8252a5c742e2aa9272fa91e71d682021-11-11T09:18:06ZAnti-Drug Antibodies in Pigtailed Macaques Receiving HIV Broadly Neutralising Antibody PGT1211664-322410.3389/fimmu.2021.749891https://doaj.org/article/099d8252a5c742e2aa9272fa91e71d682021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fimmu.2021.749891/fullhttps://doaj.org/toc/1664-3224Broadly 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.Wen Shi LeeArnold ReynaldiThakshila AmarasenaMiles P. DavenportMatthew S. ParsonsMatthew S. ParsonsMatthew S. ParsonsStephen J. KentStephen J. KentFrontiers Media S.A.articleHIVbroadly neutralizing antibodies (bNAb)PGT121anti-drug antibodies (ADA)pigtailed macaqueImmunologic diseases. AllergyRC581-607ENFrontiers in Immunology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	HIV broadly neutralizing antibodies (bNAb) PGT121 anti-drug antibodies (ADA) pigtailed macaque Immunologic diseases. Allergy RC581-607
spellingShingle	HIV broadly neutralizing antibodies (bNAb) PGT121 anti-drug antibodies (ADA) pigtailed macaque Immunologic diseases. Allergy RC581-607 Wen Shi Lee Arnold Reynaldi Thakshila Amarasena Miles P. Davenport Matthew S. Parsons Matthew S. Parsons Matthew S. Parsons Stephen J. Kent Stephen J. Kent Anti-Drug Antibodies in Pigtailed Macaques Receiving HIV Broadly Neutralising Antibody PGT121
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.
format	article
author	Wen Shi Lee Arnold Reynaldi Thakshila Amarasena Miles P. Davenport Matthew S. Parsons Matthew S. Parsons Matthew S. Parsons Stephen J. Kent Stephen J. Kent
author_facet	Wen Shi Lee Arnold Reynaldi Thakshila Amarasena Miles P. Davenport Matthew S. Parsons Matthew S. Parsons Matthew S. Parsons Stephen J. Kent Stephen J. Kent
author_sort	Wen Shi Lee
title	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_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_sort	anti-drug antibodies in pigtailed macaques receiving hiv broadly neutralising antibody pgt121
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/099d8252a5c742e2aa9272fa91e71d68
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Anti-Drug Antibodies in Pigtailed Macaques Receiving HIV Broadly Neutralising Antibody PGT121

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