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

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.

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Journal
Nature Communications
Published
2025-11-21
DOI
https://doi.org/10.1038/s41467-025-65101-7
Citations
2
Primary Topic
HIV Research and Treatment
Type
article
Field-Weighted Citation Impact
2.07

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article

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

Sheetal Sawant, David C. Montefiori, Leon R. McFarlane, Dietmar Katinger et al.
2 citations
Nature Communications
HIV Research and Treatment
2.07
article

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

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

Abstract

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.

Nature CommunicationsVol. 16(1)
Scripps Research Institute (US), Duke University (US), Cornell University (US), Karolinska Institutet (SE), Netherlands Center for Occupational Diseases (NL), Polymun (Austria) (AT), Dianet (NL), Amsterdam Neuroscience (NL), IRCCS Ospedale San Raffaele (IT), Amsterdam University Medical Centers (NL), Imperial College London (GB), University of Amsterdam (NL)
Bill and Melinda Gates Foundation, European Commission
Openalex Percentile: Top 12%
HIV Research and Treatment
2.07
DOIOpen Access PDFOpenAlex
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