TY - JOUR
T1 - HIV-1 envelope trimer vaccine induces sex-associated differences in antibody responses
T2 - a phase 1 clinical trial
AU - Reiss, Emma I. M. M.
AU - van der Straten, Karlijn
AU - Graus, Laura T. M.
AU - Grobben, Marloes
AU - Vlaming, Kilian E.
AU - van der Veen, Annelou I. P.
AU - Liesdek, Marinus H.
AU - Ozorowski, Gabriel
AU - Corcoran, Martin
AU - Gao, Hongmei
AU - Greene, Kelli M.
AU - Yates, Nicole L.
AU - Sawant, Sheetal
AU - Kerster, Gius
AU - Burger, Judith A.
AU - Schonherr, Stella
AU - Cheeseman, Hannah M.
AU - Evans, Abbey
AU - McFarlane, Leon R.
AU - Tran, Andy S.
AU - Torres, Jonathan L.
AU - Lin, Ryan N.
AU - Jo, Gyunghee
AU - Tolazzi, Monica
AU - Mundsperger, Philipp
AU - Katinger, Dietmar
AU - Cupo, Albert
AU - Moore, John P.
AU - Hurks, Rob
AU - Vogt, Liffert
AU - Soeters, Maarten R.
AU - Kootstra, Neeltje A.
AU - Scarlatti, Gabriella
AU - Tomaras, Georgia D.
AU - Montefiori, David C.
AU - Karlsson Hedestam, Gunilla B.
AU - Ward, Andrew B.
AU - Klouwens, Michelle
AU - de Jong, Menno D.
AU - Prins, Jan M.
AU - Claireaux, Mathieu
AU - Geijtenbeek, Teunis B. H.
AU - Shattock, Robin J.
AU - van Gils, Marit J.
AU - Sanders, Rogier W.
AU - de Bree, Godelieve J.
N1 - Publisher Copyright:
© The Author(s) 2025.
PY - 2025/12/1
Y1 - 2025/12/1
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/105022635559
U2 - 10.1038/s41467-025-65101-7
DO - 10.1038/s41467-025-65101-7
M3 - Article
C2 - 41271616
SN - 2041-1723
VL - 16
JO - Nat. Commun.
JF - Nat. Commun.
IS - 1
M1 - 10250
ER -