HIV-1 envelope trimer vaccine induces sex-associated differences in antibody responses: a phase 1 clinical trial
Abstract
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.
Article Details
Authors (46)
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
Duke Human Vaccine Institute, Duke University Medical Center
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
Department of Integrative Structural and Computational Biology, The Scripps Research Institute
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
Duke Human Vaccine Institute, Duke University Medical Center
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
Department of Medical Microbiology and Infection Prevention, Amsterdam Infection and Immunity Institute, Amsterdam University Medical Center, University of Amsterdam
Rogier W. Sanders
Department of Medical Microbiology and Infection Prevention, Amsterdam Infection and Immunity Institute, Amsterdam University Medical Center, University of Amsterdam
Godelieve J. de Bree