Induction of HIV-1-specific antibody-mediated effector functions by native-like envelope trimers in humans
Year: 2025
Type: article
Study design: Clinical Trial
Abstract: A protective vaccine is urgently needed to curb the ongoing global HIV-1 epidemic. There is increased interest to develop a vaccine able to induce both neutralizing antibodies and antibody-mediated effector functions for additional efficacy. We investigated the ability of a group M consensus envelope glycoprotein (Env) trimer vaccine ConM SOSIP.v7 to induce antibodies that mediate effector functions in preclinical and clinical studies. We found that the ConM SOSIP.v7 protein immunogen in combination with MPLA adjuvant induced diverse antibody-mediated effector functions in human volunteers participating in a phase 1 trial. Moreover, the functional antibody response was higher in female compared to male participants. The same immunogen induced similar antibody-mediated effector functions in preclinical studies using rabbits and non-human primates. In these preclinical models, we demonstrated that alterations in the vaccine regimen, including immunization route and adjuvant, could modulate vaccine immunogenicity and lead to functionally different antibody responses. Specifically, we observed that intramuscular immunization led to more functional antibody responses compared to subcutaneous vaccine administration, and that the MPLA liposomes and squalene emulsion adjuvants induced functionally different antibody responses. In conclusion, this study shows that HIV-1 native-like Env trimers are able to elicit antibody-mediated effector functions in humans and that preclinical studies had predictive value. Furthermore, the preclinical studies revealed that different vaccine formulations and administration routes yield qualitatively different antibody-mediated effector functions. Our findings should guide interpretation of preclinical HIV-1 vaccine studies and can inform the design of HIV-1 vaccine regimens aimed at inducing antibody-mediated effector functions in addition to neutralization capacity.
Source: PLoS Pathogens
Authors: Marloes Grobben, Emma I. M. M. Reiss, Angela I. Schriek, Karlijn van der Straten, Nathalie Dereuddre-Bosquet, Pauline Maisonnasse, Alex Rooker, Chunhao Yu, Khadija Tejjani, Monica Tolazzi, Kwinten Sliepen, Réka Felfödiné Lévai, Attila Farsang, Roger Le Grand, Gabriella Scarlatti, Robin J. Shattock, Steven W. de Taeye, Godelieve J. de Bree, Rogier W. Sanders, Marit J. van Gils
Institutions: Amsterdam University Medical Centers, Amsterdam institute for Immunology and Infectious Diseases, University of Amsterdam, Inserm, Commissariat à l'Énergie Atomique et aux Énergies Alternatives, Université Paris-Saclay, CEA Paris-Saclay - Etablissement de Fontenay-aux-roses, CEA Paris-Saclay, Infectious Disease Models and Innovative Therapies, Immunologie des Maladies Virales, Auto-immunes, Hématologiques et Bactériennes, IRCCS Ospedale San Raffaele, National Food Chain Safety Office, Imperial College London, Cornell University, Weill Cornell Medicine
Language: English
Topic: HIV Research and Treatment
Subfield: Virology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,043
Funders: Bill and Melinda Gates Foundation, Styrelsen för Internationellt Utvecklingssamarbete, Aids Fonds, Burnet Institute, European Commission, Agence Nationale de la Recherche, Nederlandse Organisatie voor Wetenschappelijk Onderzoek, Agence Nationale de Recherches sur le Sida et les Hépatites Virales, Horizon 2020
Awards: G1742836836, G1843639671, G3588224193, G434337789, G512638929, G5142169819, Infrastructure nationale pour la modélisation des maladies infectieuses humaines, G5544212856, G5802621812, G5831707436, G6042077972, European AIDS Vaccine Initiative 2020, G6237704628, G7240651115, G8510727784, European Vaccine Research and Development Infrastructure
OpenAlex ID: W4415397641