HIV vaccine candidate ΔV1gp120 formulated in ALFQA adjuvant augments mucosal immunity in female macaques

Massimiliano Bissa (), Mohammad Arif Rahman, Luca Schifanella, Katherine C. Goldfarbmuren, Isabela Silva de Castro, Emmanuel K. Woode, Anna Gutowska, Melvin N. Doster, Sophia Brown, Sarkis Sarkis, Neil R. Kanchetty, Cynthia A. Pise-Masison, Robyn Washington-Parks, Katherine McKinnon, Shraddha Basu, Jiae Kim, Ryan Alving, Dominic Paquin-Proulx, Kombo F. N’guessan, Xiaoying Shen, David C. Montefiori, Timothy Cardozo, Gary R. Matyas, Mangala Rao and Genoveffa Franchini ()
Additional contact information
Massimiliano Bissa: National Cancer Institute
Mohammad Arif Rahman: National Cancer Institute
Luca Schifanella: National Cancer Institute
Katherine C. Goldfarbmuren: Frederick National Laboratory for Cancer Research
Isabela Silva de Castro: National Cancer Institute
Emmanuel K. Woode: National Cancer Institute
Anna Gutowska: National Cancer Institute
Melvin N. Doster: National Cancer Institute
Sophia Brown: National Cancer Institute
Sarkis Sarkis: National Cancer Institute
Neil R. Kanchetty: National Cancer Institute
Cynthia A. Pise-Masison: National Cancer Institute
Robyn Washington-Parks: National Cancer Institute
Katherine McKinnon: National Cancer Institute
Shraddha Basu: Walter Reed Army Institute of Research
Jiae Kim: Walter Reed Army Institute of Research
Ryan Alving: Oak Ridge Institute of Science and Education
Dominic Paquin-Proulx: Walter Reed Army Institute of Research
Kombo F. N’guessan: Walter Reed Army Institute of Research
Xiaoying Shen: Duke University
David C. Montefiori: Duke University
Timothy Cardozo: NYU Langone Health
Gary R. Matyas: Walter Reed Army Institute of Research
Mangala Rao: Walter Reed Army Institute of Research
Genoveffa Franchini: National Cancer Institute

Nature Communications, 2025, vol. 16, issue 1, 1-20

Abstract: Abstract Simian or Human immunodeficiency virus (SIV or HIV) vaccines based on V1-deleted envelope virus-like particles, delivered by the DNA/ALVAC platforms, followed by the ΔV1gp120 boost formulated in Alum, protect 50% and 80% of macaques from mucosal infection with SIVmac251 or Simian-Human immunodeficiency virus, respectively. Adding the Army Liposome Formulation + QS21 (ALFQ) adjuvant to the ΔV1gp120+Alum boost (ALFQA) may enhance protective immune responses. Here, we show that ALFQA protects 58% of female macaques from infection following eleven exposures to SIVmac251, achieving 79% vaccine efficacy. The ALFQA vaccine regimen augments mucosal CD73+CD163+ M2-like macrophages and NKp44+ innate lymphoid cells (ILCs), while reducing NKG2A-NKP44- cells producing interferon-γ. Antibody-Dependent Cellular Cytotoxicity (ADCC) targeting helical V2, and mucosal tolerogenic dendritic cells-10 (DC-10) and envelope-specific interleukin-17+ NKp44+ ILCs, correlate with decreased risk of infection. Plasma proteome analysis links vaccine efficacy to lymphotoxin-α, mucosal DC-10, and chemokine (C-C motif) ligand-8, a chemokine produced mainly by M2-macrophages. These data support the role of pro-resolution immunity in protection afforded by the V1-deleted SIV and HIV immunogens. The Combined Long-term Efferocytosis and ADCC Responses (CLEAR) phase I HIV-vaccine trial is designed to test the safety and immunogenicity of the Alum and ALFQA adjuvants in combination with V1-deleted HIV immunogens in humans.

Date: 2025
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DOI: 10.1038/s41467-025-63610-z

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