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

Publication ,  Journal Article
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 ...
Published in: Nat Commun
February 2, 2023

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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Published In

Nat Commun

DOI

EISSN

2041-1723

Publication Date

February 2, 2023

Volume

14

Issue

1

Start / End Page

575

Location

England

Related Subject Headings

  • Vaccine Efficacy
  • Vaccination
  • Macaca mulatta
  • HIV Infections
  • HIV Envelope Protein gp120
  • HIV Antibodies
  • Female
  • Antibody-Dependent Cell Cytotoxicity
  • Animals
  • AIDS Vaccines
 

Citation

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Bissa, M., Kim, S., Galli, V., Fourati, S., Sarkis, S., Arakelyan, A., … Franchini, G. (2023). HIV vaccine candidate efficacy in female macaques mediated by cAMP-dependent efferocytosis and V2-specific ADCC. Nat Commun, 14(1), 575. https://doi.org/10.1038/s41467-023-36109-8
Bissa, Massimiliano, Sohyoung Kim, Veronica Galli, Slim Fourati, Sarkis Sarkis, Anush Arakelyan, Isabela Silva de Castro, et al. “HIV vaccine candidate efficacy in female macaques mediated by cAMP-dependent efferocytosis and V2-specific ADCC.Nat Commun 14, no. 1 (February 2, 2023): 575. https://doi.org/10.1038/s41467-023-36109-8.
Bissa M, Kim S, Galli V, Fourati S, Sarkis S, Arakelyan A, et al. HIV vaccine candidate efficacy in female macaques mediated by cAMP-dependent efferocytosis and V2-specific ADCC. Nat Commun. 2023 Feb 2;14(1):575.
Bissa, Massimiliano, et al. “HIV vaccine candidate efficacy in female macaques mediated by cAMP-dependent efferocytosis and V2-specific ADCC.Nat Commun, vol. 14, no. 1, Feb. 2023, p. 575. Pubmed, doi: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. HIV vaccine candidate efficacy in female macaques mediated by cAMP-dependent efferocytosis and V2-specific ADCC. Nat Commun. 2023 Feb 2;14(1):575.

Published In

Nat Commun

DOI

EISSN

2041-1723

Publication Date

February 2, 2023

Volume

14

Issue

1

Start / End Page

575

Location

England

Related Subject Headings

  • Vaccine Efficacy
  • Vaccination
  • Macaca mulatta
  • HIV Infections
  • HIV Envelope Protein gp120
  • HIV Antibodies
  • Female
  • Antibody-Dependent Cell Cytotoxicity
  • Animals
  • AIDS Vaccines