ADCC-mediating non-neutralizing antibodies can exert immune pressure in early HIV-1 infection.

Despite antibody-dependent cellular cytotoxicity (ADCC) responses being implicated in protection from HIV-1 infection, there is limited evidence that they control virus replication. The high mutability of HIV-1 enables the virus to rapidly adapt, and thus evidence of viral escape is a very sensitive...

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Autores principales:	Dieter Mielke, Gama Bandawe, Jie Zheng, Jennifer Jones, Melissa-Rose Abrahams, Valerie Bekker, Christina Ochsenbauer, Nigel Garrett, Salim Abdool Karim, Penny L Moore, Lynn Morris, David Montefiori, Colin Anthony, Guido Ferrari, Carolyn Williamson
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/5a3db5562c124425bf5699df1bb930c9
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spelling	oai:doaj.org-article:5a3db5562c124425bf5699df1bb930c92021-12-02T19:59:52ZADCC-mediating non-neutralizing antibodies can exert immune pressure in early HIV-1 infection.1553-73661553-737410.1371/journal.ppat.1010046https://doaj.org/article/5a3db5562c124425bf5699df1bb930c92021-11-01T00:00:00Zhttps://doi.org/10.1371/journal.ppat.1010046https://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Despite antibody-dependent cellular cytotoxicity (ADCC) responses being implicated in protection from HIV-1 infection, there is limited evidence that they control virus replication. The high mutability of HIV-1 enables the virus to rapidly adapt, and thus evidence of viral escape is a very sensitive approach to demonstrate the importance of this response. To enable us to deconvolute ADCC escape from neutralizing antibody (nAb) escape, we identified individuals soon after infection with detectable ADCC responses, but no nAb responses. We evaluated the kinetics of ADCC and nAb responses, and viral escape, in five recently HIV-1-infected individuals. In one individual we detected viruses that escaped from ADCC responses but were sensitive to nAbs. In the remaining four participants, we did not find evidence of viral evolution exclusively associated with ADCC-mediating non-neutralizing Abs (nnAbs). However, in all individuals escape from nAbs was rapid, occurred at very low titers, and in three of five cases we found evidence of viral escape before detectable nAb responses. These data show that ADCC-mediating nnAbs can drive immune escape in early infection, but that nAbs were far more effective. This suggests that if ADCC responses have a protective role, their impact is limited after systemic virus dissemination.Dieter MielkeGama BandaweJie ZhengJennifer JonesMelissa-Rose AbrahamsValerie BekkerChristina OchsenbauerNigel GarrettSalim Abdool KarimPenny L MooreLynn MorrisDavid MontefioriColin AnthonyGuido FerrariCarolyn WilliamsonPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 17, Iss 11, p e1010046 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Dieter Mielke Gama Bandawe Jie Zheng Jennifer Jones Melissa-Rose Abrahams Valerie Bekker Christina Ochsenbauer Nigel Garrett Salim Abdool Karim Penny L Moore Lynn Morris David Montefiori Colin Anthony Guido Ferrari Carolyn Williamson ADCC-mediating non-neutralizing antibodies can exert immune pressure in early HIV-1 infection.
description	Despite antibody-dependent cellular cytotoxicity (ADCC) responses being implicated in protection from HIV-1 infection, there is limited evidence that they control virus replication. The high mutability of HIV-1 enables the virus to rapidly adapt, and thus evidence of viral escape is a very sensitive approach to demonstrate the importance of this response. To enable us to deconvolute ADCC escape from neutralizing antibody (nAb) escape, we identified individuals soon after infection with detectable ADCC responses, but no nAb responses. We evaluated the kinetics of ADCC and nAb responses, and viral escape, in five recently HIV-1-infected individuals. In one individual we detected viruses that escaped from ADCC responses but were sensitive to nAbs. In the remaining four participants, we did not find evidence of viral evolution exclusively associated with ADCC-mediating non-neutralizing Abs (nnAbs). However, in all individuals escape from nAbs was rapid, occurred at very low titers, and in three of five cases we found evidence of viral escape before detectable nAb responses. These data show that ADCC-mediating nnAbs can drive immune escape in early infection, but that nAbs were far more effective. This suggests that if ADCC responses have a protective role, their impact is limited after systemic virus dissemination.
format	article
author	Dieter Mielke Gama Bandawe Jie Zheng Jennifer Jones Melissa-Rose Abrahams Valerie Bekker Christina Ochsenbauer Nigel Garrett Salim Abdool Karim Penny L Moore Lynn Morris David Montefiori Colin Anthony Guido Ferrari Carolyn Williamson
author_facet	Dieter Mielke Gama Bandawe Jie Zheng Jennifer Jones Melissa-Rose Abrahams Valerie Bekker Christina Ochsenbauer Nigel Garrett Salim Abdool Karim Penny L Moore Lynn Morris David Montefiori Colin Anthony Guido Ferrari Carolyn Williamson
author_sort	Dieter Mielke
title	ADCC-mediating non-neutralizing antibodies can exert immune pressure in early HIV-1 infection.
title_short	ADCC-mediating non-neutralizing antibodies can exert immune pressure in early HIV-1 infection.
title_full	ADCC-mediating non-neutralizing antibodies can exert immune pressure in early HIV-1 infection.
title_fullStr	ADCC-mediating non-neutralizing antibodies can exert immune pressure in early HIV-1 infection.
title_full_unstemmed	ADCC-mediating non-neutralizing antibodies can exert immune pressure in early HIV-1 infection.
title_sort	adcc-mediating non-neutralizing antibodies can exert immune pressure in early hiv-1 infection.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/5a3db5562c124425bf5699df1bb930c9
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ADCC-mediating non-neutralizing antibodies can exert immune pressure in early HIV-1 infection.

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