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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| Format: | Article |
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Frontiers Media S.A.
2021-11-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2021.749891/full |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-20T22:34:22Z |
| format | Article |
| id | doaj.art-099d8252a5c742e2aa9272fa91e71d68 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-20T22:34:22Z |
| publishDate | 2021-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-099d8252a5c742e2aa9272fa91e71d682022-12-21T19:24:38ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-11-011210.3389/fimmu.2021.749891749891Anti-Drug Antibodies in Pigtailed Macaques Receiving HIV Broadly Neutralising Antibody PGT121Wen Shi Lee0Arnold Reynaldi1Thakshila Amarasena2Miles P. Davenport3Matthew S. Parsons4Matthew S. Parsons5Matthew S. Parsons6Stephen J. Kent7Stephen J. Kent8Department of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, VIC, AustraliaKirby Institute, University of New South Wales, Kensington, NSW, AustraliaDepartment of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, VIC, AustraliaKirby Institute, University of New South Wales, Kensington, NSW, AustraliaDepartment of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, VIC, AustraliaDepartment of Pathology and Laboratory Medicine, School of Medicine, Emory University, Atlanta, GA, United StatesYerkes National Primate Research Center, Emory University, Atlanta, GA, United StatesDepartment of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, VIC, AustraliaMelbourne Sexual Health Centre and Department of Infectious Diseases, Central Clinical School, Monash University, Melbourne, VIC, AustraliaBroadly 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.https://www.frontiersin.org/articles/10.3389/fimmu.2021.749891/fullHIVbroadly neutralizing antibodies (bNAb)PGT121anti-drug antibodies (ADA)pigtailed macaque |
| spellingShingle | 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 Frontiers in Immunology HIV broadly neutralizing antibodies (bNAb) PGT121 anti-drug antibodies (ADA) pigtailed macaque |
| 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 | HIV broadly neutralizing antibodies (bNAb) PGT121 anti-drug antibodies (ADA) pigtailed macaque |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2021.749891/full |
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