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

Author

Listed:
  • 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
    Emory 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
    Tulane National Primate Research Center, Tulane University)

  • Jeffrey A. Tomalka

    (Case Western Reserve University
    Emory 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
    Vaccine Branch Flow Cytometry Core, 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
    Emory 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)

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.

Suggested Citation

  • 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, 2023. "HIV vaccine candidate efficacy in female macaques mediated by cAMP-dependent efferocytosis and V2-specific ADCC," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-36109-8
    DOI: 10.1038/s41467-023-36109-8
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    References listed on IDEAS

    as
    1. Irinna Papangeli & Jongmin Kim & Inna Maier & Saejeong Park & Aram Lee & Yujung Kang & Keiichiro Tanaka & Omar F. Khan & Hyekyung Ju & Yoko Kojima & Kristy Red-Horse & Daniel G. Anderson & Arndt F. Si, 2016. "MicroRNA 139-5p coordinates APLNR-CXCR4 crosstalk during vascular maturation," Nature Communications, Nature, vol. 7(1), pages 1-11, September.
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