1. Comparative immunogenicity of an mRNA/LNP and a DNA vaccine targeting HIV gag conserved elements in macaques
- Author
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Valentin, Antonio, Bergamaschi, Cristina, Rosati, Margherita, Angel, Matthew, Burns, Robert, Agarwal, Mahesh, Gergen, Janina, Petsch, Benjamin, Oostvogels, Lidia, Loeliger, Edde, Chew, Kara W, Deeks, Steven G, Mullins, James I, Pavlakis, George N, and Felber, Barbara K
- Subjects
Medical Microbiology ,Biomedical and Clinical Sciences ,Immunology ,Prevention ,Biotechnology ,Vaccine Related ,Infectious Diseases ,Vaccine Related (AIDS) ,Genetics ,HIV/AIDS ,Immunization ,Development of treatments and therapeutic interventions ,Prevention of disease and conditions ,and promotion of well-being ,3.4 Vaccines ,5.1 Pharmaceuticals ,Infection ,Inflammatory and immune system ,Good Health and Well Being ,AIDS Vaccines ,Animals ,CD8-Positive T-Lymphocytes ,HIV Infections ,HIV-1 ,Liposomes ,Macaca mulatta ,Nanoparticles ,RNA ,Messenger ,Vaccines ,DNA ,Vaccines ,Synthetic ,mRNA Vaccines ,mRNA ,LNP ,therapeutic immunization ,HIV ,T cell response ,antibody ,gag ,conserved sequences ,immune focusing ,mRNA/LNP ,Biochemistry and cell biology - Abstract
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 gag 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 gag mRNA/LNP efficiently boosted both humoral and cellular responses in macaques previously primed by a gag DNA-based vaccine. These anamnestic cellular responses were mediated by activated CD8+ T cells with a phenotype of differentiated T-bet+ 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.
- Published
- 2022