학술논문
HIV vaccine candidate efficacy in female macaques mediated by cAMP-dependent efferocytosis and V2-specific ADCC
Document Type
Original Paper
Author
Bissa, Massimiliano; Kim, Sohyoung; Galli, Veronica; Fourati, Slim; Sarkis, Sarkis; Arakelyan, Anush; de Castro, Isabela Silva; Rahman, Mohammad Arif; Fujiwara, Saori; Vaccari, Monica; Tomalka, Jeffrey A.; Stamos, James D.; Schifanella, Luca; Gorini, Giacomo; Moles, Ramona; Gutowska, Anna; Ferrari, Guido; Lobanov, Alexei; Montefiori, David C.; Nelson, George W.; Cam, Margaret C.; Chakhtoura, Marita; Haddad, Elias K.; Doster, Melvin N.; McKinnon, Katherine; Brown, Sophia; Venzon, David J.; Choo-Wosoba, Hyoyoung; Breed, Matthew W.; Killoran, Kristin E.; Kramer, Joshua; Margolis, Leonid; Sekaly, Rafick P.; Hager, Gordon L.; Franchini, Genoveffa
Source
Nature Communications. 14(1)
Subject
Language
English
ISSN
2041-1723
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.
HIV vaccine development can be aided by knowledge of correlates of protection. Here the authors identify engagement and reprogramming of tolerogenic CD14+ myeloid cells mediating a spatiotemporal balance of pro- and anti-inflammatory responses, as correlates of efficacy in female macaques vaccinated with the DNA/ALVAC/gp120/Alum platform.
HIV vaccine development can be aided by knowledge of correlates of protection. Here the authors identify engagement and reprogramming of tolerogenic CD14