NK cell depletion in bispecific antibody therapy is associated with lack of HIV control after ART interruption
Sánchez-Gaona, Nerea (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Perea, David (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Curran, A. (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Burgos, J. (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Navarro, Jordi (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Suanzes, Paula (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Falcó, Vicenç (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Martín Gayo, Enrique (Universidad Autónoma de Madrid)
Genescà Ferrer, Meritxell (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Carrillo, Jorge (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Buzón, Maria José (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Universitat Autònoma de Barcelona

Date:	2025
Abstract:	HIV infection remains incurable as the virus persists within a latent reservoir of CD4 + T cells. Novel approaches to enhance immune responses against HIV are essential for effective control and potential cure of the infection. In this study, we designed a novel tetravalent bispecific antibody (Bi-Ab32/16) to simultaneously target the gp120 viral protein on infected cells, and the CD16a receptor on NK cells. In vitro, Bi-Ab32/16 triggered a potent, specific, and polyfunctional NK-dependent response against HIV-infected cells. Moreover, addition of the Bi-Ab32/16 significantly reduced the latent HIV reservoir after viral reactivation and mediated the clearance of cells harboring intact proviruses in samples from people with HIV (PWH). However, the in vivo preclinical evaluation of Bi-Ab32/16 in humanized mice expressing IL-15 (NSG-Hu-IL-15) revealed a significant decline of NK cells associated with poor virological control after ART interruption. Our study underscores the need to carefully evaluating strategies for sustained NK cell stimulation during ART withdrawal. Bispecific antibody targeting NK cells facilitates clearance of HIV-infected cells in vitro but poses challenges in sustaining NK cell function during ART withdrawal in preclinical models.
Grants:	Agencia Estatal de Investigación RTI2018-101082-B-I00 Agencia Estatal de Investigación PID2021-123321OB-I00 Instituto de Salud Carlos III PI20/00160
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	HIV infections ; Viral reservoirs
Published in:	Communications Biology, Vol. 8 (february 2025) , ISSN 2399-3642

DOI: 10.1038/s42003-025-07651-6
PMID: 39953264

16 p, 4.6 MB

The record appears in these collections:
Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP)
Articles > Research articles
Articles > Published articles