Comparative immunogenicity of an mRNA/LNP and a DNA vaccine targeting HIV gag conserved elements in macaques.

Autor:	Valentin A; Human Retrovirus Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, MD, United States., Bergamaschi C; Human Retrovirus Pathogenesis Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, MD, United States., Rosati M; Human Retrovirus Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, MD, United States., Angel M; Vaccine Branch, Center for Cancer Research, National Cncer Institute, Bethesda, MD, United States.; Center for Cancer Research Collaborative Bioinformatics Resource, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD, United States., Burns R; Human Retrovirus Pathogenesis Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, MD, United States., Agarwal M; Human Retrovirus Pathogenesis Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, MD, United States., Gergen J; CureVac AG, Tübingen, Germany., Petsch B; CureVac AG, Tübingen, Germany., Oostvogels L; CureVac AG, Tübingen, Germany., Loeliger E; CureVac AG, Tübingen, Germany., Chew KW; Department of Medicine, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA, United States., Deeks SG; Division of HIV, Infectious Diseases and Global Medicine, University of California, San Francisco, CA, United States., Mullins JI; Department of Microbiology, University of Washington, Seattle, WA, United States.; Department of Medicine, University of Washington, Seattle, WA, United States.; Department of Global Health, University of Washington, Seattle, WA, United States., Pavlakis GN; Human Retrovirus Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, MD, United States., Felber BK; Human Retrovirus Pathogenesis Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, MD, United States.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2022 Jul 22; Vol. 13, pp. 945706. Date of Electronic Publication: 2022 Jul 22 (Print Publication: 2022).
DOI:	10.3389/fimmu.2022.945706
Abstrakt:	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. Competing Interests: Authors JM, GP, BP and BF report issued patents of relevance to this work. Author MAn was employed by Leidos Biomedical Research, Inc. Authors JG, BP, LO, EL are employed by CureVac AG. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Valentin, Bergamaschi, Rosati, Angel, Burns, Agarwal, Gergen, Petsch, Oostvogels, Loeliger, Chew, Deeks, Mullins, Pavlakis and Felber.)
Databáze:	MEDLINE
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