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

Nat Commun. 2023 Feb 2;14(1):575. doi: 10.1038/s41467-023-36109-8.

Authors

Massimiliano Bissa¹, Sohyoung Kim², Veronica Galli³, Slim Fourati^{4

5}, Sarkis Sarkis³, Anush Arakelyan⁶, Isabela Silva de Castro³, Mohammad Arif Rahman³, Saori Fujiwara², Monica Vaccari^{3

7}, Jeffrey A Tomalka^{4

5}, James D Stamos³, Luca Schifanella³, Giacomo Gorini³, Ramona Moles³, Anna Gutowska³, Guido Ferrari⁸, Alexei Lobanov⁹, David C Montefiori⁸, George W Nelson⁹, Margaret C Cam⁹, Marita Chakhtoura¹⁰, Elias K Haddad¹⁰, Melvin N Doster³, Katherine McKinnon¹¹, Sophia Brown^{3

11}, David J Venzon¹², Hyoyoung Choo-Wosoba¹², Matthew W Breed¹³, Kristin E Killoran¹³, Joshua Kramer¹³, Leonid Margolis⁶, Rafick P Sekaly^{4

5}, Gordon L Hager², Genoveffa Franchini¹⁴

Affiliations

¹ Animal Models and Retroviral Vaccines Section, National Cancer Institute, Bethesda, MD, USA. massimiliano.bissa@nih.gov.
² Laboratory of Receptor Biology and Gene Expression, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
³ Animal Models and Retroviral Vaccines Section, National Cancer Institute, Bethesda, MD, USA.
⁴ Department of Pathology, Case Western Reserve University, Cleveland, OH, USA.
⁵ Department of Pathology, Emory University, Atlanta, GA, USA.
⁶ Section on Intercellular Interactions, Eunice Kennedy-Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA.
⁷ Tulane National Primate Research Center, Tulane University, Covington, LA, USA.
⁸ Division of Surgical Sciences, Duke University School of Medicine, Durham, NC, USA.
⁹ Collaborative Bioinformatics Resource, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
¹⁰ Department of Medicine, Drexel University College of Medicine, Philadelphia, PA, USA.
¹¹ Vaccine Branch Flow Cytometry Core, National Cancer Institute, Bethesda, MD, USA.
¹² Biostatistics and Data Management Section, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
¹³ Laboratory Animal Sciences Program, Leidos Biomedical Research Inc., Frederick National Laboratory, Frederick, MD, USA.
¹⁴ Animal Models and Retroviral Vaccines Section, National Cancer Institute, Bethesda, MD, USA. franchig@mail.nih.gov.

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.

Publication types

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

MeSH terms

AIDS Vaccines*
Animals
Antibody-Dependent Cell Cytotoxicity
Female
HIV Antibodies
HIV Envelope Protein gp120 / genetics
HIV Infections* / prevention & control
Macaca mulatta
Vaccination
Vaccine Efficacy

Substances

AIDS Vaccines
HIV Antibodies
HIV Envelope Protein gp120

Abstract

Publication types

MeSH terms

Substances

Grants and funding