Safety, tolerability, and immunogenicity of a recombinant toxic shock syndrome toxin (rTSST)-1 variant vaccine: a randomised, double-blind, adjuvant-controlled, dose escalation first-in-man trial

Summary Background Staphylococcal toxic shock syndrome is a superantigen-driven potentially life-threatening disease affecting mainly young and otherwise healthy individuals. Currently, no specific treatment or preventive measure is available. We aimed to assess the safety, tolerability, and immunogenicity of a recombinant detoxified toxic shock syndrome toxin-1 variant (rTSST-1v) vaccine in adult volunteers. Methods In this randomised, double-blind, adjuvant-controlled, dose-escalation first-in-human trial, healthy adults aged 18–64 years were enrolled from the Medical University of Vienna, Austria. Participants were randomly assigned (2:1 and 3:1) by block randomisation (block sizes of three and 12) to receive increasing doses of rTSST-1v (100 ng to 30 μg) or the adjuvant comparator aluminium hydroxide (Al(OH) 3 ) (200 μg, 600 μg, or 1 mg). Investigators and participants were masked to group allocation. The per-protocol population received a booster immunisation 42 days after the first vaccination. The primary endpoint was safety and tolerability of rTSST-1v. The per-protocol population included all participants who had adhered to the study protocol without any major protocol deviations. The per-protocol population was the primary analysis population for immunogenicity. The trial is registered with EudraCT, number 2013-003716-50, and ClinicalTrials.gov, number NCT02340338. Findings Between Aug 19, 2014, and April 14, 2015, 46 participants were enrolled (safety population), of whom three were assigned to cohort 1 (two to receive 100 ng rTSST-1v and one to receive 200 μg Al(OH) 3 ), three to cohort 2 (two to receive 300 ng rTSST-1v and one to receive 600 μg Al(OH) 3 ), four to cohort 3 (three to receive 1 μg rTSST-1v and one to receive 1 mg Al(OH) 3 ), 12 to cohort 4 (nine to receive 3 μg rTSST-1v and three to receive 1 mg Al(OH) 3 ), 12 to cohort 5 (nine to receive 10 μg rTSST-1v and three to receive 1 mg Al(OH) 3 ), and 12 to cohort 6 (nine to receive 300 μg rTSST-1v and three to receive 1 mg Al(OH) 3 ). 45 participants (98%) were included in the per-protocol population. rTSST-1v had a good safety profile, and no vaccination-related severe or serious adverse events occurred. Adverse event rates were similar between participants who received rTSST-1v and those who received placebo (26 [76%] vs 10 [83%]; p=0·62) independent of pre-existing TSST-1 immunity. Interpretation rTSST-1v was safe, well-tolerated, and immunogenic. This study represents an important step in vaccine development to prevent or treat a potentially lethal disease. Funding Biomedizinische Forschungs GmbH.