Increased immunogen valency improves the maturation of vaccine-elicited HIV-1 VRC01-like antibodies
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Le résumé fourni par la source
Antibodies belonging to the VRC01-class display broad and potent neutralizing activities and have been isolated from several people living with HIV (PLWH). A member of that class, monoclonal antibody VRC01, was shown to reduce HIV-acquisition in two phase 2b efficacy trials. VRC01-class antibodies are therefore expected to be one component of an effective HIV-1 vaccine elicited response. In contrast to the VRC01-class antibodies that are highly mutated, their unmutated forms do not engage HIV-1 envelope (Env) and do not display neutralizing activities. Hence, specifically modified Env-derived proteins have been designed to engage the unmutated forms of VRC01-class antibodies, and to activate the corresponding naïve B cells. Selected heterologous Env must then be used as boost immunogens to guide the proper maturation of these elicited VRC01-class antibodies. Here we examined whether and how the valency of the prime and boost immunogens influences VRC01-class antibody-maturation. Our findings indicate that, indeed the valency of the immunogen affects the maturation of elicited antibody responses by preferentially selecting VRC01-like antibodies that have accumulated somatic mutations present in broadly neutralizing VRC01-class antibodies isolated from PLWH. As a result, antibodies isolated from animals immunized with the higher valency immunogens display broader Env cross-binding properties and improved neutralizing potentials than those isolated from animals immunized with the lower valency immunogens. Our results are relevant to current and upcoming phase 1 clinical trials that evaluate the ability of novel immunogens aiming to elicit cross-reactive VRC01-class antibody responses.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Increased immunogen valency improves the maturation of vaccine-elicited HIV-1 VRC01-like antibodies
- Date Crossref
- 29/05/2025
- Éditeur
- Public Library of Science (PLoS)
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Fred Hutch Cancer Center pays non établi dans la noticeOrganisation à but non lucratif
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Duke Medical Center pays non établi dans la noticeÉtablissement de santé
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Howard Hughes Medical Institute pays non établi dans la noticeStructure de recherche
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University of Washington Department of Genome Sciences pays non établi dans la noticeUniversité ou école supérieure
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Vaccine and Infectious Disease Division pays non établi dans la noticeInstitution
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Computational Biology Program pays non établi dans la noticeInstitution
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Translational Science and Therapeutics Division pays non établi dans la noticeInstitution
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Duke University Medical Center Division of Surgical Sciences pays non établi dans la noticeUniversité ou école supérieure
Fred Hutch Cancer Center, Duke Medical Center et Howard Hughes Medical Institute, avec 5 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.