HIV-1 envelope trimer vaccine induces sex-associated differences in antibody responses: a phase 1 clinical trial
- 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
2025-11-21
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.