A randomized, double-blind study on the safety and immunogenicity of rTSST-1 variant vaccine: phase 2 results

• Published in: EClinicalMedicine 2024-01, Vol.67, p.102404, Article 102404
• Main Authors: Schoergenhofer, Christian, Gelbenegger, Georg, Hasanacevic, Dzenita, Schöner, Léa, Steiner, Margarete M., Firbas, Christa, Buchtele, Nina, Derhaschnig, Ulla, Tanzmann, Andreas, Model, Nina, Larcher-Senn, Julian, Drost, Manuel, Eibl, Martha M., Roetzer, Andreas, Jilma, Bernd
• Format: Article
• Language: English
• Subjects: Staphylococcus aureus; Superantigen; Toxic shock syndrome; TSST-1; Vaccine
• ISSN: 2589-5370; 2589-5370
• DOI: 10.1016/j.eclinm.2023.102404

Toxic shock syndrome toxin-1 (TSST-1) is a superantigen produced by Staphylococcus aureus that causes the life-threatening toxic shock syndrome. The development of a safe and immunogenic vaccine against TSST-1 remains an unmet medical need. We investigated the safety, tolerability and immunogenicity of a recombinant TSST-1 variant vaccine (rTSST-1v) after 1–3 injections in healthy volunteers. In this randomised, double-blind, adjuvant-controlled, parallel-group, phase 2 trial, healthy adults aged 18–64 were randomly allocated to undergo 1–3 injections of either 10 or 100 μg rTSST-1v or Al(OH)3. The primary endpoint was safety and tolerability of rTSST-1v in the intention-to-treat population. The per-protocol population was used for the immunogenicity analysis. The trial is registered with EudraCT#: 2015-003714-24; ClinicalTrials.gov#: NCT02814708. Between April and November 2017,140 subjects were enrolled and 126 completed the trial. rTSST-1v showed a good safety and tolerability profile. A total of 855 systemic adverse events occurred, 280 of which were suspected related adverse events, without dose dependency. Two participants were discontinued early because of allergic reactions. Seroconversion occurred in >81% of subjects within 3 months of the first immunisation which was sustained until 18 months after the third immunisation in over 70% of subjects in the pooled low-dose group and in over 85% in the pooled high-dose group. rTSST-1v in cumulative doses of up to 300 μg was safe, well-tolerated and highly immunogenic. Two immunisations with 100 μg rTSST-1v provided the most persistent immune response and may be evaluated in future trials. Biomedizinische Forschung & Bio-Produkte AG funded this study.