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 de 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. NelsonMargaret 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, Genoveffa Franchini*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

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.

Original languageEnglish (US)
Article number575
JournalNature communications
Volume14
Issue number1
DOIs
StatePublished - Dec 2023

ASJC Scopus subject areas

  • General Chemistry
  • General Biochemistry, Genetics and Molecular Biology
  • General Physics and Astronomy

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