Year: 2026
Type: article
Abstract: ABSTRACT Restoring effective antiviral immunity remains a major challenge in HIV infection. Emerging immune checkpoint leukocyte immunoglobulin‐like receptor B1 (LILRB1) and LILRB2 have been proposed as therapeutic targets, yet their in vivo function remains undefined due to the lack of cross‐reactive blocking antibodies for relevant preclinical models. Here, we developed a dual‐specific blocking monoclonal antibody, mac20G10, targeting cynomolgus macaque LILRB1 and LILRB2 and assessed its immunomodulatory activity in an SIV model of infection. Pharmacodynamic analyses demonstrated that mac20G10 persisted in circulation and engaged target myeloid cells for up to 14 days without detectable adverse effects. A single administration prior to SIVmac251 infection enhanced early myeloid immune activation, characterized by increased frequencies of CD80 + plasmacytoid dendritic cells (pDCs) and CD80 + monocyte/macrophage subsets in blood and lymphoid tissues. These changes were accompanied by increased plasma levels of interferon lambda (IFN‐λ), IL‐8, and IL‐1RA during acute infection. Although viral replication remained unchanged, mac20G10 treatment promoted the development of SIV‐specific memory CD8 + T‐cell responses. Together, these data show that LILRB1/B2 blockade modulates early myeloid activation and is associated with enhanced SIV‐specific memory CD8+ T‐cell responses. These findings support further evaluation of LILRB1/B2 blockade as part of combination immunotherapeutic strategies in settings such as ART‐treated infection and analytical treatment interruption.
Source: Advanced Science
DOI: 10.1002/advs.76557
Authors: Florian Meurisse, Sixtine Coindre, Anne Wijkhuisen, Romain Marlin, Laure Fournier Le Ray, Juliette Pons, Melyssa Yaugel‐Novoa, Véronique Avettand‐Fenoel, Laurent Abi‐Rached, Anne‐Sophie Gallouet, Francis Relouzat, Mael Gourves, Asier Saez‐Cirion, Hisashi Arase, Gerard Zurawski, Sandra Zurawski, Nathalie Dereuddre‐Bosquet, Roger Le Grand, Stéphanie Simon, Olivier Lambotte, Benoit Favier
Institutions: Inserm, Commissariat à l'Énergie Atomique et aux Énergies Alternatives, Université Paris-Saclay, CEA Paris-Saclay - Etablissement de Fontenay-aux-roses, Infectious Disease Models and Innovative Therapies, Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement, Médicaments et Technologies pour la Santé, Université d'Orléans, Centre hospitalier universitaire d'Orléans, Centre National de la Recherche Scientifique, Aix-Marseille Université, Méditerranée Infection Foundation, Institut Pasteur, Université Paris Cité, The University of Osaka, Assistance Publique – Hôpitaux de Paris, Bicêtre Hospital
Language: English
Topic: HIV Research and Treatment
Subfield: Virology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $6,730
Awards: G1190173965, PRE-CLINICAL STUDY OF A NEW IMMUNE-CHECKPOINT INHIBITOR IN SARS-COV-2 INFECTION, G1961185104, G5142169819, Infrastructure nationale pour la modélisation des maladies infectieuses humaines, G5802621812, G6237704628, G7240651115, aPpROche par Médecine de prEcision pour la prise en charge THérapeutique du sEpsis commUnautaire et lié aux Soins, G8510727784
OpenAlex ID: W7171809952