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/fd1a9e56d1df41cf85ae7238ccf3f401
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spelling	oai:doaj.org-article:fd1a9e56d1df41cf85ae7238ccf3f4012021-11-25T05:47:33ZADCC-mediating non-neutralizing antibodies can exert immune pressure in early HIV-1 infection1553-73661553-7374https://doaj.org/article/fd1a9e56d1df41cf85ae7238ccf3f4012021-11-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8598021/?tool=EBIhttps://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. Author summary Reponses that clear or control viral replication in acute infection are considered important responses to elicit by vaccination. In the only HIV-1 vaccine trial to date to show any efficacy, antibody-dependent cellular cytotoxicity (ADCC)-mediating non-neutralizing antibodies (nnAbs) were correlated with reduced risk of infection. However, the role of ADCC-mediating antibodies in controlling replication in acute infection is not well understood. Viral escape provides evidence of the importance of immune responses, but there is very little evidence of HIV-1 immune escape from nnAbs to-date. We assessed the impact of early ADCC-mediating nnAbs on HIV-1 envelope evolution in infected individuals where we had early samples, prior to the detection of nAbs. We found evidence of escape from ADCC-mediating nnAbs, but in only one individual. In contrast, escape to nAbs was rapid and with or without resistance to ADCC-mediating antibodies. We identified escape pathways which were sensitive to neutralization but resistant to ADCC. These data show that ADCC-mediating nnAbs can drive immune escape in early infection, but to a lesser extent than nAbs, suggesting they may have a limited protective role 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 (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. Author summary Reponses that clear or control viral replication in acute infection are considered important responses to elicit by vaccination. In the only HIV-1 vaccine trial to date to show any efficacy, antibody-dependent cellular cytotoxicity (ADCC)-mediating non-neutralizing antibodies (nnAbs) were correlated with reduced risk of infection. However, the role of ADCC-mediating antibodies in controlling replication in acute infection is not well understood. Viral escape provides evidence of the importance of immune responses, but there is very little evidence of HIV-1 immune escape from nnAbs to-date. We assessed the impact of early ADCC-mediating nnAbs on HIV-1 envelope evolution in infected individuals where we had early samples, prior to the detection of nAbs. We found evidence of escape from ADCC-mediating nnAbs, but in only one individual. In contrast, escape to nAbs was rapid and with or without resistance to ADCC-mediating antibodies. We identified escape pathways which were sensitive to neutralization but resistant to ADCC. These data show that ADCC-mediating nnAbs can drive immune escape in early infection, but to a lesser extent than nAbs, suggesting they may have a limited protective role 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/fd1a9e56d1df41cf85ae7238ccf3f401
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ADCC-mediating non-neutralizing antibodies can exert immune pressure in early HIV-1 infection

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