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 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 J. 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
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.