HIV vaccine candidate ΔV1gp120 formulated in ALFQA adjuvant augments mucosal immunity in female macaques
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 SIV<sub>mac251</sub> 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 SIV<sub>mac251</sub>, achieving 79% vaccine efficacy. The ALFQA vaccine regimen augments mucosal CD73<sup>+</sup>CD163<sup>+</sup> M2-like macrophages and NKp44<sup>+</sup> innate lymphoid cells (ILCs), while reducing NKG2A<sup>-</sup>NKP44<sup>-</sup> 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<sup>+</sup> NKp44<sup>+</sup> 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.
Authors
- Luca Schifanella (ORCID: https://orcid.org/0000-0002-6123-536X)
- David C. Montefiori (ORCID: https://orcid.org/0000-0003-0856-6319)
- Sophia Brown (ORCID: https://orcid.org/0000-0001-5782-8755)
- Cynthia A. Pise-Masison (ORCID: https://orcid.org/0000-0003-2788-235X)
- Gary R. Matyas (ORCID: https://orcid.org/0000-0002-2074-2373)
- Dominic Paquin‐Proulx (ORCID: https://orcid.org/0000-0003-1407-3414)
- Kombo F. N’guessan
- Anna Gutowska (ORCID: https://orcid.org/0000-0002-9873-6432)
- Isabela Silva de Castro (ORCID: https://orcid.org/0000-0003-2186-4556)
- Xiaoying Shen (ORCID: https://orcid.org/0000-0002-8387-3952)
- Genoveffa Franchini (ORCID: https://orcid.org/0000-0003-2851-6589)
- Massimiliano Bissa (ORCID: https://orcid.org/0000-0003-3455-3992)
- Melvin N. Doster
- Katherine C. Goldfarbmuren (ORCID: https://orcid.org/0000-0001-8774-7454)
- Shraddha Basu
- Mohammad Arif Rahman (ORCID: https://orcid.org/0000-0002-6120-8943)
- Timothy Cardozo (ORCID: https://orcid.org/0000-0002-0643-4497)
- Katherine McKinnon (ORCID: https://orcid.org/0000-0002-8281-3077)
- Robyn Washington‐Parks (ORCID: https://orcid.org/0000-0002-5284-9765)
- Jiae Kim (ORCID: https://orcid.org/0000-0003-2900-1667)
- Mangala Rao (ORCID: https://orcid.org/0000-0001-9553-4969)
- Emmanuel K. Woode
- Sarkis Sarkis (ORCID: https://orcid.org/0000-0002-4355-6338)
- Neil R. Kanchetty
- Ryan Alving
Institutions
- Henry M. Jackson Foundation (US)
- Oak Ridge Associated Universities (US)
- National Institutes of Health (US)
- Duke University (US)
- NYU Langone Health (US)
- Frederick National Laboratory for Cancer Research (US)
- National Cancer Institute (US)
- Center for Cancer Research (US)
- New York University (US)
- Walter Reed Army Institute of Research (US)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-09-29
- DOI
- https://doi.org/10.1038/s41467-025-63610-z
- Primary Topic
- HIV Research and Treatment
- Type
- article
- Field-Weighted Citation Impact
- 0.00