JOURNAL ARTICLE
RANDOMIZED CONTROLLED TRIAL

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

Michael Schwameis, Bernhard Roppenser, Christa Firbas, Corina S Gruener, Nina Model, Norbert Stich, Andreas Roetzer, Nina Buchtele, Bernd Jilma, Martha M Eibl
Lancet Infectious Diseases 2016, 16 (9): 1036-1044
27296693

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.

Full Text Links

Find Full Text Links for this Article

Discussion

You are not logged in. Sign Up or Log In to join the discussion.

Related Papers

Remove bar
Read by QxMD icon Read
27296693
×

Save your favorite articles in one place with a free QxMD account.

×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"

We want to hear from doctors like you!

Take a second to answer a survey question.