Three families of CD4-induced antibodies are associated with the capacity of plasma from people living with HIV to mediate ADCC in presence of CD4-mimetics

Alexandra Tauzin; Lorie Marchitto; Étienne Bélanger; Mehdi Benlarbi; Guillaume Beaudoin-Bussières; Jérémie Prévost; Derek Yang; Ta-Jung Chiu; Hung-Ching Chen; Catherine Bourassa; Halima Medjahed; Marek K Korzeniowski; Suneetha Gottumukkala; William D Tolbert; Jonathan Richard; Amos B Smith 3rd; Marzena Pazgier; Andrés Finzi

doi:10.1101/2024.06.02.24308281

Three families of CD4-induced antibodies are associated with the capacity of plasma from people living with HIV to mediate ADCC in presence of CD4-mimetics

medRxiv [Preprint]. 2024 Jun 4:2024.06.02.24308281. doi: 10.1101/2024.06.02.24308281.

Authors

Alexandra Tauzin^{1

2}, Lorie Marchitto^{1

2}, Étienne Bélanger^{1

2}, Mehdi Benlarbi^{1

2}, Guillaume Beaudoin-Bussières^{1

2}, Jérémie Prévost^{1

2}, Derek Yang³, Ta-Jung Chiu³, Hung-Ching Chen³, Catherine Bourassa¹, Halima Medjahed¹, Marek K Korzeniowski⁴, Suneetha Gottumukkala⁴, William D Tolbert⁴, Jonathan Richard^{1

2}, Amos B Smith 3rd³, Marzena Pazgier⁴, Andrés Finzi^{1

2}

Affiliations

¹ Centre de Recherche du CHUM, Montreal, QC, Canada.
² Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montreal, QC, Canada.
³ Department of Chemistry, School of Arts and Sciences, University of Pennsylvania, Philadelphia, PA, USA.
⁴ Infectious Diseases Division, Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.

Abstract

CD4-mimetics (CD4mcs) are small molecule compounds that mimic the interaction of the CD4 receptor with HIV-1 envelope glycoproteins (Env). Env from primary viruses normally samples a "closed" conformation which occludes epitopes recognized by CD4-induced (CD4i) non-neutralizing antibodies (nnAbs). CD4mcs induce conformational changes on Env resulting in the exposure of these otherwise inaccessible epitopes. Here we evaluated the capacity of plasma from a cohort of 50 people living with HIV to recognize HIV-1-infected cells and eliminate them by antibody-dependent cellular cytotoxicity (ADCC) in the presence of a potent indoline CD4mc. We observed a marked heterogeneity among plasma samples. By measuring the levels of different families of CD4i Abs, we found that the levels of anti-cluster A, anti-coreceptor binding site and anti-gp41 cluster I antibodies are responsible for plasma-mediated ADCC in presence of CD4mc.

Publication types

Preprint

Abstract

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