{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T09:12:27Z","timestamp":1791364347193,"version":"4.3.1"},"reference-count":100,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,7,22]],"date-time":"2022-07-22T00:00:00Z","timestamp":1658448000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Immunogenicity of HIV-1 mRNA vaccine regimens was analyzed in a non-human primate animal model. Rhesus macaques immunized with mRNA in lipid nanoparticle (mRNA\/LNP) formulation expressing HIV-1 Gag and Gag conserved regions (CE) as immunogens developed robust, durable antibody responses but low adaptive T-cell responses. Augmentation of the dose resulted in modest increases in vaccine-induced cellular immunity, with no difference in humoral responses. The <jats:italic>gag<\/jats:italic> mRNA\/lipid nanoparticle (LNP) vaccine provided suboptimal priming of T cell responses for a heterologous DNA booster vaccination regimen. In contrast, a single immunization with <jats:italic>gag<\/jats:italic> mRNA\/LNP efficiently boosted both humoral and cellular responses in macaques previously primed by a <jats:italic>gag<\/jats:italic> DNA-based vaccine. These anamnestic cellular responses were mediated by activated CD8<jats:sup>+<\/jats:sup> T cells with a phenotype of differentiated T-bet<jats:sup>+<\/jats:sup> cytotoxic memory T lymphocytes. The heterologous prime\/boost regimens combining DNA and mRNA\/LNP vaccine modalities maximized vaccine-induced cellular and humoral immune responses. Analysis of cytokine responses revealed a transient systemic signature characterized by the release of type I interferon, IL-15 and IFN-related chemokines. The pro-inflammatory status induced by the mRNA\/LNP vaccine was also characterized by IL-23 and IL-6, concomitant with the release of IL-17 family of cytokines. Overall, the strong boost of cellular and humoral immunity induced by the mRNA\/LNP vaccine suggests that it could be useful as a prophylactic vaccine in heterologous prime\/boost modality and in immune therapeutic interventions against HIV infection or other chronic human diseases.<\/jats:p>","DOI":"10.3389\/fimmu.2022.945706","type":"journal-article","created":{"date-parts":[[2022,7,23]],"date-time":"2022-07-23T05:39:00Z","timestamp":1658554740000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":31,"title":["Comparative immunogenicity of an mRNA\/LNP and a DNA vaccine targeting HIV gag conserved elements in 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