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. 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; Genoveffa Franchini

doi:10.1038/s41467-023-36109-8

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

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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 language	English (US)
Article number	575
Journal	Nature communications
Volume	14
Issue number	1
DOIs	https://doi.org/10.1038/s41467-023-36109-8
State	Published - Dec 2023

Bibliographical note

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.

PubMed: MeSH publication types

Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/s41467-023-36109-8

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Bissa, M., Kim, S., Galli, V., Fourati, S., Sarkis, S., Arakelyan, A., de Castro, I. S., Rahman, M. A., Fujiwara, S., Vaccari, M., Tomalka, J. A., Stamos, J. D., Schifanella, L., Gorini, G., Moles, R., Gutowska, A., Ferrari, G., Lobanov, A., Montefiori, D. C., ... Franchini, G. (2023). HIV vaccine candidate efficacy in female macaques mediated by cAMP-dependent efferocytosis and V2-specific ADCC. Nature communications, 14(1), Article 575. https://doi.org/10.1038/s41467-023-36109-8

Bissa, M, Kim, S, Galli, V, Fourati, S, Sarkis, S, Arakelyan, A, de Castro, IS, Rahman, MA, Fujiwara, S, Vaccari, M, Tomalka, JA, Stamos, JD, Schifanella, L, Gorini, G, Moles, R, Gutowska, A, Ferrari, G, Lobanov, A, Montefiori, DC, Nelson, GW, Cam, MC, Chakhtoura, M, Haddad, EK, Doster, MN, McKinnon, K, Brown, S, Venzon, DJ, Choo-Wosoba, H, Breed, MW, Killoran, KE, Kramer, J, Margolis, L, Sekaly, RP, Hager, GL & Franchini, G 2023, 'HIV vaccine candidate efficacy in female macaques mediated by cAMP-dependent efferocytosis and V2-specific ADCC', Nature communications, vol. 14, no. 1, 575. https://doi.org/10.1038/s41467-023-36109-8

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

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.",

author = "Massimiliano Bissa and Sohyoung Kim and Veronica Galli and Slim Fourati and Sarkis Sarkis and Anush Arakelyan and {de Castro}, {Isabela Silva} and Rahman, {Mohammad Arif} and Saori Fujiwara and Monica Vaccari and Tomalka, {Jeffrey A.} and Stamos, {James D.} and Luca Schifanella and Giacomo Gorini and Ramona Moles and Anna Gutowska and Guido Ferrari and Alexei Lobanov and Montefiori, {David C.} and Nelson, {George W.} and Cam, {Margaret C.} and Marita Chakhtoura and Haddad, {Elias K.} and Doster, {Melvin N.} and Katherine McKinnon and Sophia Brown and Venzon, {David J.} and Hyoyoung Choo-Wosoba and Breed, {Matthew W.} and Killoran, {Kristin E.} and Joshua Kramer and Leonid Margolis and Sekaly, {Rafick P.} and Hager, {Gordon L.} and Genoveffa Franchini",

note = "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: {\textcopyright} 2023, This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.",

year = "2023",

month = dec,

doi = "10.1038/s41467-023-36109-8",

language = "English (US)",

volume = "14",

journal = "Nature communications",

issn = "2041-1723",

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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.

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JF - Nature communications

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

Abstract

Bibliographical note

PubMed: MeSH publication types

UN SDGs

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