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 () and Godelieve J. de Bree ()
Additional contact information
Emma I. M. M. Reiss: Amsterdam UMC, location University of Amsterdam, Department of Medical Microbiology and Infection prevention
Karlijn van der Straten: Amsterdam UMC, location University of Amsterdam, Department of Medical Microbiology and Infection prevention
Laura T. M. Graus: Amsterdam UMC, location University of Amsterdam, Department of Medical Microbiology and Infection prevention
Marloes Grobben: Amsterdam UMC, location University of Amsterdam, Department of Medical Microbiology and Infection prevention
Kilian E. Vlaming: Amsterdam Institute for Immunology and Infectious Diseases
Annelou I. P. van der Veen: Amsterdam Institute for Immunology and Infectious Diseases
Marinus H. Liesdek: Amsterdam UMC, location University of Amsterdam, Department of Medical Microbiology and Infection prevention
Gabriel Ozorowski: The Scripps Research Institute, Department of Integrative Structural and Computational Biology
Martin Corcoran: Karolinska Institutet, Department of Microbiology, Tumor and Cell Biology
Hongmei Gao: Duke University School of Medicine, Department of Surgery
Kelli M. Greene: Duke University School of Medicine, Department of Surgery
Nicole L. Yates: Duke University School of Medicine, Department of Surgery
Sheetal Sawant: Duke University School of Medicine, Department of Surgery
Gius Kerster: Amsterdam UMC, location University of Amsterdam, Department of Medical Microbiology and Infection prevention
Judith A. Burger: Amsterdam UMC, location University of Amsterdam, Department of Medical Microbiology and Infection prevention
Stella Schonherr: Amsterdam Institute for Immunology and Infectious Diseases
Hannah M. Cheeseman: Technology and Medicine, Group of Mucosal Infection and Immunity, Department of Infectious Disease, Imperial College of Science
Abbey Evans: Technology and Medicine, Group of Mucosal Infection and Immunity, Department of Infectious Disease, Imperial College of Science
Leon R. McFarlane: Technology and Medicine, Group of Mucosal Infection and Immunity, Department of Infectious Disease, Imperial College of Science
Andy S. Tran: The Scripps Research Institute, Department of Integrative Structural and Computational Biology
Jonathan L. Torres: The Scripps Research Institute, Department of Integrative Structural and Computational Biology
Ryan N. Lin: The Scripps Research Institute, Department of Integrative Structural and Computational Biology
Gyunghee Jo: The Scripps Research Institute, Department of Integrative Structural and Computational Biology
Monica Tolazzi: IRCCS Ospedale San Raffaele, Viral Evolution and Transmission Unit, Division of Immunology, Transplantation and Infectious Diseases
Philipp Mundsperger: Polymun Scientific Immunbiologische Forschung GmbH
Dietmar Katinger: Polymun Scientific Immunbiologische Forschung GmbH
Albert Cupo: Weill Medical College of Cornell University, Department of Microbiology and Immunology
John P. Moore: Weill Medical College of Cornell University, Department of Microbiology and Immunology
Rob Hurks: University of Amsterdam, Department of Radiology, Amsterdam UMC
Liffert Vogt: Amsterdam UMC, location University of Amsterdam, Department of Internal Medicine
Maarten R. Soeters: Amsterdam UMC, location University of Amsterdam, Department of Internal Medicine
Neeltje A. Kootstra: Amsterdam Institute for Immunology and Infectious Diseases
Gabriella Scarlatti: IRCCS Ospedale San Raffaele, Viral Evolution and Transmission Unit, Division of Immunology, Transplantation and Infectious Diseases
Georgia D. Tomaras: Duke University School of Medicine, Department of Surgery
David C. Montefiori: Duke University School of Medicine, Department of Surgery
Gunilla B. Karlsson Hedestam: Karolinska Institutet, Department of Microbiology, Tumor and Cell Biology
Andrew B. Ward: The Scripps Research Institute, Department of Integrative Structural and Computational Biology
Michelle Klouwens: Amsterdam Institute for Immunology and Infectious Diseases
Menno D. de Jong: Amsterdam UMC, location University of Amsterdam, Department of Medical Microbiology and Infection prevention
Jan M. Prins: Amsterdam Institute for Immunology and Infectious Diseases
Mathieu Claireaux: Amsterdam UMC, location University of Amsterdam, Department of Medical Microbiology and Infection prevention
Teunis B. H. Geijtenbeek: Amsterdam Institute for Immunology and Infectious Diseases
Robin J. Shattock: Technology and Medicine, Group of Mucosal Infection and Immunity, Department of Infectious Disease, Imperial College of Science
Marit J. van Gils: Amsterdam UMC, location University of Amsterdam, Department of Medical Microbiology and Infection prevention
Rogier W. Sanders: Amsterdam UMC, location University of Amsterdam, Department of Medical Microbiology and Infection prevention
Godelieve J. de Bree: Amsterdam UMC, location University of Amsterdam, Department of Internal Medicine

Nature Communications, 2025, vol. 16, issue 1, 1-16

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.

Date: 2025
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-025-65101-7 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-65101-7

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-025-65101-7

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().