HIV vaccine candidate efficacy in female macaques mediated by cAMP-dependent efferocytosis and V2-specific ADCC

Massimiliano Bissa (), Sohyoung Kim, Veronica Galli, Slim Fourati, Sarkis Sarkis, Anush Arakelyan, Isabela Silva Castro, Mohammad Arif Rahman, Saori Fujiwara, Monica Vaccari, Jeffrey A. Tomalka, James D. Stamos, Luca Schifanella, Giacomo Gorini, Ramona Moles, Anna Gutowska, Guido Ferrari, Alexei Lobanov, David C. Montefiori, George W. Nelson, Margaret C. Cam, Marita Chakhtoura, Elias K. Haddad, Melvin N. Doster, Katherine McKinnon, Sophia Brown, David J. Venzon, Hyoyoung Choo-Wosoba, Matthew W. Breed, Kristin E. Killoran, Joshua Kramer, Leonid Margolis, Rafick P. Sekaly, Gordon L. Hager and Genoveffa Franchini ()
Additional contact information
Massimiliano Bissa: Animal Models and Retroviral Vaccines Section, National Cancer Institute
Sohyoung Kim: Laboratory of Receptor Biology and Gene Expression, National Cancer Institute, National Institutes of Health
Veronica Galli: Animal Models and Retroviral Vaccines Section, National Cancer Institute
Slim Fourati: Case Western Reserve University
Sarkis Sarkis: Animal Models and Retroviral Vaccines Section, National Cancer Institute
Anush Arakelyan: Section on Intercellular Interactions, Eunice Kennedy-Shriver National Institute of Child Health and Human Development, National Institutes of Health
Isabela Silva Castro: Animal Models and Retroviral Vaccines Section, National Cancer Institute
Mohammad Arif Rahman: Animal Models and Retroviral Vaccines Section, National Cancer Institute
Saori Fujiwara: Laboratory of Receptor Biology and Gene Expression, National Cancer Institute, National Institutes of Health
Monica Vaccari: Animal Models and Retroviral Vaccines Section, National Cancer Institute
Jeffrey A. Tomalka: Case Western Reserve University
James D. Stamos: Animal Models and Retroviral Vaccines Section, National Cancer Institute
Luca Schifanella: Animal Models and Retroviral Vaccines Section, National Cancer Institute
Giacomo Gorini: Animal Models and Retroviral Vaccines Section, National Cancer Institute
Ramona Moles: Animal Models and Retroviral Vaccines Section, National Cancer Institute
Anna Gutowska: Animal Models and Retroviral Vaccines Section, National Cancer Institute
Guido Ferrari: Duke University School of Medicine
Alexei Lobanov: Collaborative Bioinformatics Resource, Center for Cancer Research, National Cancer Institute
David C. Montefiori: Duke University School of Medicine
George W. Nelson: Collaborative Bioinformatics Resource, Center for Cancer Research, National Cancer Institute
Margaret C. Cam: Collaborative Bioinformatics Resource, Center for Cancer Research, National Cancer Institute
Marita Chakhtoura: Drexel University College of Medicine
Elias K. Haddad: Drexel University College of Medicine
Melvin N. Doster: Animal Models and Retroviral Vaccines Section, National Cancer Institute
Katherine McKinnon: Vaccine Branch Flow Cytometry Core, National Cancer Institute
Sophia Brown: Animal Models and Retroviral Vaccines Section, National Cancer Institute
David J. Venzon: Biostatistics and Data Management Section, Center for Cancer Research, National Cancer Institute
Hyoyoung Choo-Wosoba: Biostatistics and Data Management Section, Center for Cancer Research, National Cancer Institute
Matthew W. Breed: Laboratory Animal Sciences Program, Leidos Biomedical Research Inc., Frederick National Laboratory
Kristin E. Killoran: Laboratory Animal Sciences Program, Leidos Biomedical Research Inc., Frederick National Laboratory
Joshua Kramer: Laboratory Animal Sciences Program, Leidos Biomedical Research Inc., Frederick National Laboratory
Leonid Margolis: Section on Intercellular Interactions, Eunice Kennedy-Shriver National Institute of Child Health and Human Development, National Institutes of Health
Rafick P. Sekaly: Case Western Reserve University
Gordon L. Hager: Laboratory of Receptor Biology and Gene Expression, National Cancer Institute, National Institutes of Health
Genoveffa Franchini: Animal Models and Retroviral Vaccines Section, National Cancer Institute

Nature Communications, 2023, vol. 14, issue 1, 1-19

Abstract: Abstract The development of an effective vaccine to protect against HIV acquisition will be greatly bolstered by in-depth understanding of the innate and adaptive responses to vaccination. We report here that the efficacy of DNA/ALVAC/gp120/alum vaccines, based on V2-specific antibodies mediating apoptosis of infected cells (V2-ADCC), is complemented by efferocytosis, a cyclic AMP (cAMP)-dependent antiphlogistic engulfment of apoptotic cells by CD14+ monocytes. Central to vaccine efficacy is the engagement of the CCL2/CCR2 axis and tolerogenic dendritic cells producing IL-10 (DC-10). Epigenetic reprogramming in CD14+ cells of the cyclic AMP/CREB pathway and increased systemic levels of miRNA-139-5p, a negative regulator of expression of the cAMP-specific phosphodiesterase PDE4D, correlated with vaccine efficacy. These data posit that efferocytosis, through the prompt and effective removal of apoptotic infected cells, contributes to vaccine efficacy by decreasing inflammation and maintaining tissue homeostasis.

Date: 2023
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DOI: 10.1038/s41467-023-36109-8

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