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Safety and Immunogenicity of a Recombinant Toxic Shock Syndrome Toxin (rTSST)-1 Variant Vaccine: A Randomised, Double-Blind, Adjuvant-Controlled, Parallel-Group, Phase 2 Trial
77 Pages Posted: 3 Nov 2023
More...Abstract
Background: 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.
Methods: 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 100µg 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.
Findings: Of 140 enrolled subjects, 126 completed the trial (per-protocol analysis). 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.
Interpretation: 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.
Trial Registration: EudraCT 2015-003714-24, clinicaltrials.gov (NCT02814708).
Funding: This research was funded by Biomedizinische Forschung & Bio-Produkte AG.
Declaration of Interest: GG, CS, CF, MMS, NB, UD, AT, and BJ declare no competing interests. Martha M. Eibl was the owner of Biomedizinische Forschung & Bio-Produkte AG. DH, LS, NM, and AR are employees of the study funder Biomedizinische Forschung & Bio- Produkte AG, a biotechnology company engaged in the development of BioMed rTSST-1v.
Ethical Approval: The study was approved by the local ethics committee (Ethics Committee of the Medical University of Vienna, European Research Council Number 1810/2015) and was conducted in compliance with the Declaration of Helsinki, the Good Clinical Practice guidelines and with the Note for Guidance on Clinical Evaluation of New Vaccines. Oral and written informed consent was obtained prior to any trial-related procedure.
Keywords: Staphylococcus aureus, toxic shock syndrome, superantigen, TSST-1, vaccine
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