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<p>A protective vaccine will be the most powerful instrument to reduce HIV-1 infections worldwide and help bring about a lasting end to the AIDS epidemic. The single centre, randomised, open-label, uncontrolled, phase 1 ACTHIVE-001 clinical trial (NCT03961438) aims to assess the safety and immunogenicity of the ConM SOSIP.v7 native-like trimer protein vaccine, based on an HIV-1 group M consensus sequence, in HIV-negative adults. Twenty-four individuals were enrolled to receive three dosages of ConM SOSIP.v7 protein vaccine in a liposome formulation containing a high dose of the TLR4-agonist MPLA. The primary outcome is vaccine reactogenicity, whereas the main secondary outcome is binding and neutralising antibody responses. Overall, the vaccine is safe and well-tolerated. Furthermore, the vaccine elicits robust strain-specific binding and neutralising antibody responses in nearly all vaccinees. Post-hoc exploratory analyses demonstrate that female-born participants have 22- and 6-fold higher neutralisation titres after the second and third vaccination, respectively. The vaccine adjuvant induces higher levels of IL-6 secretion from in vitro cultured monocytes from female compared to male participants, providing a possible mechanistic explanation for the sex-based differences. Our study highlights the need to take sex-based differences into consideration when assessing HIV-1 vaccine candidates and adjuvants.</p>

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HIV-1 envelope trimer vaccine induces sex-associated differences in antibody responses: a phase 1 clinical trial

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年11月21日

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  • Emma I. M. M. Reiss,
  • Karlijn van der Straten,
  • Laura T. M. Graus,
  • Marloes Grobben,
  • Kilian E. Vlaming,
  • Annelou I. P. van der Veen,
  • Marinus H. Liesdek,
  • Gabriel Ozorowski,
  • Martin Corcoran,
  • Hongmei Gao,
  • Kelli M. Greene,
  • Nicole L. Yates,
  • Sheetal Sawant,
  • Gius Kerster,
  • Judith A. Burger,
  • Stella Schonherr,
  • Hannah M. Cheeseman,
  • Abbey Evans,
  • Leon R. McFarlane,
  • Andy S. Tran,
  • Jonathan L. Torres,
  • Ryan N. Lin,
  • Gyunghee Jo,
  • Monica Tolazzi,
  • Philipp Mundsperger,
  • Dietmar Katinger,
  • Albert Cupo,
  • John P. Moore,
  • Rob Hurks,
  • Liffert Vogt,
  • Maarten R. Soeters,
  • Neeltje A. Kootstra,
  • Gabriella Scarlatti,
  • Georgia D. Tomaras,
  • David C. Montefiori,
  • Gunilla B. Karlsson Hedestam,
  • Andrew B. Ward,
  • Michelle Klouwens,
  • Menno D. de Jong,
  • Jan M. Prins,
  • Mathieu Claireaux,
  • Teunis B. H. Geijtenbeek,
  • Robin J. Shattock,
  • Marit J. van Gils,
  • Rogier W. Sanders,
  • Godelieve J. de Bree

摘要

A protective vaccine will be the most powerful instrument to reduce HIV-1 infections worldwide and help bring about a lasting end to the AIDS epidemic. The single centre, randomised, open-label, uncontrolled, phase 1 ACTHIVE-001 clinical trial (NCT03961438) aims to assess the safety and immunogenicity of the ConM SOSIP.v7 native-like trimer protein vaccine, based on an HIV-1 group M consensus sequence, in HIV-negative adults. Twenty-four individuals were enrolled to receive three dosages of ConM SOSIP.v7 protein vaccine in a liposome formulation containing a high dose of the TLR4-agonist MPLA. The primary outcome is vaccine reactogenicity, whereas the main secondary outcome is binding and neutralising antibody responses. Overall, the vaccine is safe and well-tolerated. Furthermore, the vaccine elicits robust strain-specific binding and neutralising antibody responses in nearly all vaccinees. Post-hoc exploratory analyses demonstrate that female-born participants have 22- and 6-fold higher neutralisation titres after the second and third vaccination, respectively. The vaccine adjuvant induces higher levels of IL-6 secretion from in vitro cultured monocytes from female compared to male participants, providing a possible mechanistic explanation for the sex-based differences. Our study highlights the need to take sex-based differences into consideration when assessing HIV-1 vaccine candidates and adjuvants.