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<p>Adjuvants play an important role in modulating antigen-specific immune responses. We conducted a comparative adjuvant immunogenicity study in Rhesus macaques using HIV-1 subtype B gp120 envelope protein, B.63521, formulated with aluminum hydroxide gel (AH), or a family of liposomal adjuvants known as Army Liposome Formulation (ALF). ALF comprises saturated phospholipids, cholesterol, and monophosphoryl lipid A. Inclusion of QS-21 or adsorption of the antigen to AH, followed by the addition of ALF, generates ALFQ and ALFA, while inclusion of both immunostimulants generates ALFQA. Priming with canarypox vector ALVAC, followed by boosting with ALVAC and gp120 formulated with each of the four adjuvants, resulted in ALFQ and ALFQA outperforming AH and ALFA vaccine formulations with a high frequency of antigen-specific plasma cells in the bone marrow, robust antibodies, and Env-specific polyfunctional CD8<sup>+</sup> T cell responses. Transcriptomic analyses revealed upregulation of antiviral and innate immune pathways, thus highlighting ALFQ as a highly potent adjuvant.</p>

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ALFQ adjuvanted HIV-1 envelope protein vaccination elicits durable functional antibody and cellular responses in nonhuman primates

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月19日

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  • Shikha Shrivastava,
  • Joshua M. Carmen,
  • Jiae Kim,
  • Kristina K. Peachman,
  • Shraddha Basu,
  • Ryan Alving,
  • Danielle Nettere,
  • Gautam Kundu,
  • Lauren Yum,
  • Mohammad Arif Rahman,
  • Shalini Jha,
  • Hung V. Trinh,
  • Lorean Rosado,
  • Phuong Nguyen,
  • Elaine Morrison,
  • Isabella Swafford,
  • Kawthar Machmach,
  • Jessica S. Bolton,
  • Adam Yates,
  • Elina Misicka,
  • Zoltan Beck,
  • Simona Mutascio,
  • Ousman Jobe,
  • Michelle Zemil McCrea,
  • Lindsay Wieczorek,
  • Elke S. Bergmann-Leitner,
  • Victoria Polonis,
  • Dominic Paquin-Proulx,
  • Justin Pollara,
  • Gary R. Matyas,
  • Carl R. Alving,
  • Rasmi Thomas,
  • Genoveffa Franchini,
  • Guido Ferrari,
  • Barton F. Haynes,
  • Julie A. Ake,
  • Mangala Rao

摘要

Adjuvants play an important role in modulating antigen-specific immune responses. We conducted a comparative adjuvant immunogenicity study in Rhesus macaques using HIV-1 subtype B gp120 envelope protein, B.63521, formulated with aluminum hydroxide gel (AH), or a family of liposomal adjuvants known as Army Liposome Formulation (ALF). ALF comprises saturated phospholipids, cholesterol, and monophosphoryl lipid A. Inclusion of QS-21 or adsorption of the antigen to AH, followed by the addition of ALF, generates ALFQ and ALFA, while inclusion of both immunostimulants generates ALFQA. Priming with canarypox vector ALVAC, followed by boosting with ALVAC and gp120 formulated with each of the four adjuvants, resulted in ALFQ and ALFQA outperforming AH and ALFA vaccine formulations with a high frequency of antigen-specific plasma cells in the bone marrow, robust antibodies, and Env-specific polyfunctional CD8+ T cell responses. Transcriptomic analyses revealed upregulation of antiviral and innate immune pathways, thus highlighting ALFQ as a highly potent adjuvant.