{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T06:31:29Z","timestamp":1765175489002,"version":"3.46.0"},"reference-count":75,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T00:00:00Z","timestamp":1765152000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000738","name":"U.S. Department of Veterans Affairs","doi-asserted-by":"publisher","award":["I01BX005616, IK6BX004607"],"award-info":[{"award-number":["I01BX005616, IK6BX004607"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AI139290, AI148327, AI140909, AI179427, AI145655, P01AI172531, AI160706, AI180874, AI176069"],"award-info":[{"award-number":["AI139290, AI148327, AI140909, AI179427, AI145655, P01AI172531, AI160706, AI180874, AI176069"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Despite decades of research, the development of an effective HIV vaccine remains a significant challenge. Recent findings from three large vaccine efficacy trials have identified antibodies against the V1V2 domain of the HIV envelope glycoprotein as a potential correlate of reduced infection risk, offering a promising avenue for improving vaccine efficacy. Vaccine-elicited anti-V1V2 antibodies do not mediate potent virus-neutralizing activities, but they mediate Fc-dependent effector functions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This study evaluated the capacity of V1V2-scaffold vaccines in different formulations to generate antibody responses with Fc-mediated functions. BALB\/c mice were immunized with V1V2-scaffold proteins formulated with one of the following adjuvants: MF59-like squalene-based oil-in-water emulsion (Addavax), a combination of TLR7\/8 and RIG-I agonists (IMDQ-PC\/IVT), nanoemulsion and RIG-I agonist (NE\/IVT), or empty lipid nanoparticles (eLNP). All formulations were administered intramuscularly except NE\/IVT, which was given intranasally. For comparison, we also tested a V1V2-scaffold-expressing mRNA-LNP vaccine delivered intramuscularly and an Env gp140 protein with liposomal MPLA\/DDA adjuvant administered subcutaneously.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Among the six vaccine formulations tested, V1V2-scaffold immunogens adjuvanted with LNP (eLNP and mRNA-LNP) elicited the most robust and cross-reactive serum IgG responses that recognized native Env on cell surfaces or virions. The eLNP and mRNA-LNP groups, along with IMDQ-PC\/IVT, also elicited functional IgG2a, and correspondingly displayed Fc-mediated activities, as measured by antibody-dependent cellular phagocytosis and Fc\u03b3RIV binding. Notably, IMDQ-PC\/IVT elicited predominantly IgG2a with minimal IgG1, eLNP stimulated IgG1 and IgG2a with IgG1 dominance, whereas mRNA-LNP yielded more balanced IgG2a\/IgG1 responses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Data from this study provide new insights into the utility of novel formulations for V1V2-scaffold immunogens as a strategy for optimizing the induction of functional V1V2-specific antibodies to improve HIV vaccine efficacy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2025.1722596","type":"journal-article","created":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T06:29:16Z","timestamp":1765175356000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Enhancing functional antibody responses against HIV envelope V1V2 through vaccine 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