TY - JOUR
T1 - HIV vaccine candidate efficacy in female macaques mediated by cAMP-dependent efferocytosis and V2-specific ADCC
AU - Bissa, Massimiliano
AU - Kim, Sohyoung
AU - Galli, Veronica
AU - Fourati, Slim
AU - Sarkis, Sarkis
AU - Arakelyan, Anush
AU - de Castro, Isabela Silva
AU - Rahman, Mohammad Arif
AU - Fujiwara, Saori
AU - Vaccari, Monica
AU - Tomalka, Jeffrey A.
AU - Stamos, James D.
AU - Schifanella, Luca
AU - Gorini, Giacomo
AU - Moles, Ramona
AU - Gutowska, Anna
AU - Ferrari, Guido
AU - Lobanov, Alexei
AU - Montefiori, David C.
AU - Nelson, George W.
AU - Cam, Margaret C.
AU - Chakhtoura, Marita
AU - Haddad, Elias K.
AU - Doster, Melvin N.
AU - McKinnon, Katherine
AU - Brown, Sophia
AU - Venzon, David J.
AU - Choo-Wosoba, Hyoyoung
AU - Breed, Matthew W.
AU - Killoran, Kristin E.
AU - Kramer, Joshua
AU - Margolis, Leonid
AU - Sekaly, Rafick P.
AU - Hager, Gordon L.
AU - Franchini, Genoveffa
N1 - Funding Information:
We thank David Ahern for editorial assistance. We thank Nancy Miller and John Warren (NIAID) for support for part of the animal studies and discussion, Tom Misteli (NCI) for critical reading of the manuscript, James Tartaglia (Sanofi Pasteur) for critical reading of the manuscript and for the ALVAC-SIV vaccine, George N. Pavlakis, Barbara K. Felber, and Margherita Rosati (NCI), for the SIV gag and gp160 wild type DNA vaccines used in Study 1 and the SIV gag DNA vaccine used in Study 2, and Matthew Angel (NCI) for help with miRNA analyses. TZM-bl cells were obtained from the NIH AIDS Research and Reference Reagent Program, contributed by John Kappes and Xiaoyun Wu. This work was supported with federal funds from the National Cancer Institute Intramural Program and the Office of AIDS research, National Institutes of Health (to G. Franchini). Whole blood transcriptome analysis was supported by Collaboration for Aids Vaccine Discovery (CAVD) grant OPP1147555 from the Bill and Melinda Gates Foundation (to R-P. Sekaly). ADCC and neutralization analyses were supported by NIAID contract number HHSN272201800004C (Duke University; PI, Xiaoying Shen) The contents of this publication do not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement.
Funding Information:
We thank David Ahern for editorial assistance. We thank Nancy Miller and John Warren (NIAID) for support for part of the animal studies and discussion, Tom Misteli (NCI) for critical reading of the manuscript, James Tartaglia (Sanofi Pasteur) for critical reading of the manuscript and for the ALVAC-SIV vaccine, George N. Pavlakis, Barbara K. Felber, and Margherita Rosati (NCI), for the SIV gag and gp160 wild type DNA vaccines used in Study 1 and the SIV gag DNA vaccine used in Study 2, and Matthew Angel (NCI) for help with miRNA analyses. TZM-bl cells were obtained from the NIH AIDS Research and Reference Reagent Program, contributed by John Kappes and Xiaoyun Wu. This work was supported with federal funds from the National Cancer Institute Intramural Program and the Office of AIDS research, National Institutes of Health (to G. Franchini). Whole blood transcriptome analysis was supported by Collaboration for Aids Vaccine Discovery (CAVD) grant OPP1147555 from the Bill and Melinda Gates Foundation (to R-P. Sekaly). ADCC and neutralization analyses were supported by NIAID contract number HHSN272201800004C (Duke University; PI, Xiaoying Shen) The contents of this publication do not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement.
Publisher Copyright:
© 2023, This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.
PY - 2023/12
Y1 - 2023/12
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85147318859&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85147318859&partnerID=8YFLogxK
U2 - 10.1038/s41467-023-36109-8
DO - 10.1038/s41467-023-36109-8
M3 - Article
C2 - 36732510
AN - SCOPUS:85147318859
SN - 2041-1723
VL - 14
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 575
ER -
