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

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• 作者：Michael Schwameis ; MD^a ; ^&dagger ; ; Bernhard Roppenser ; PhD^b ; ^&dagger ; ; Christa Firbas ; MD^a ; Corina S Gruener ; Msc^b ; Nina Model ; VMD^b ; Norbert Stich ; PhD^b ; Andreas Roetzer ; PhD^b ; Nina Buchtele ; cand.med^a ; Prof Bernd Jilma ; MD^a ; ^{bernd.jilma@meduniwien.ac.at" class="auth_mail" title="E-mail the corresponding author} ; Prof Martha M Eibl ; MD^b ; ^{martha.eibl@meduniwien.ac.at" class="auth_mail" title="E-mail the corresponding author}
• 刊名：The Lancet Infectious Diseases
• 出版年：2016
• 出版时间：September 2016
• 年：2016
• 卷：16
• 期：9
• 页码：1036-1044
• 全文大小：380 K

文摘

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.