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<p>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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年9月29日

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  • 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,
  • Genoveffa Franchini

摘要

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.