Antibody-Dependent Cellular Cytotoxicity-Competent Antibodies against HIV-1-Infected Cells in Plasma from HIV-Infected Subjects

Author:

Dupuy Franck P.12,Kant Sanket123,Barbé Alexandre1,Routy Jean-Pierre12345,Bruneau Julie67,Lebouché Bertrand1258,Tremblay Cécile79,Pazgier Marzena10,Finzi Andrés7911,Bernard Nicole F.123512

Affiliation:

1. Research Institute of the McGill University Health Centre (RI-MUHC), Montreal, Quebec, Canada

2. Infectious Diseases and Immunity in Global Health Program, RI-MUHC, Montreal, Quebec, Canada

3. Division of Experimental Medicine, McGill University, Montreal, Quebec, Canada

4. Division of Hematology, McGill University Health Centre, Montreal, Quebec, Canada

5. Chronic Viral Illness Service, McGill University Health Centre, Montreal, Quebec, Canada

6. Department of Family Medicine, Université de Montréal, Montreal, Quebec, Canada

7. Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CRCHUM), Montreal, Quebec, Canada

8. Department of Family Medicine, McGill University, Montreal, Quebec, Canada

9. Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montreal, Quebec, Canada

10. Infectious Diseases Division, Department of Medicine of Uniformed Services, University of the Health Sciences, Bethesda, Maryland, USA

11. Department of Microbiology and Immunology, McGill University, Montreal, Quebec, Canada

12. Division of Clinical Immunology, McGill University Health Centre, Montreal, Quebec, Canada

Abstract

HIV Env-specific nonneutralizing Abs (NnAbs) able to mediate ADCC have been implicated in protection from HIV infection. However, Env-specific NnAbs have the capacity to support ADCC of both HIV-infected and HIV-uninfected bystander cells, potentially leading to misinterpretations when the assay used to measure ADCC does not distinguish between the two target cell types present in HIV cultures. Using a novel ADCC assay, which simultaneously quantifies the killing activity of Env-specific Abs on both infected and uninfected bystander cells, we observed that only a minority of Env-specific Abs in HIV + plasma mediated ADCC of genuinely HIV-infected cells displaying Env in its native closed conformation. This assay can be used for the development of vaccine strategies aimed at eliciting Env-specific Ab responses capable of controlling HIV infection.

Funder

Canadian Institutes for Health Research

Fonds de Recherche du Quebec - Santé

HHS | National Institutes of Health

Publisher

American Society for Microbiology

Subject

Virology,Microbiology

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