A randomized, double-blind study on the safety and immunogenicity of rTSST-1 variant vaccine : phase 2 results
© 2024 Published by Elsevier Ltd..
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 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.
Findings: 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.
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.
Funding: Biomedizinische Forschung & Bio-Produkte AG funded this study.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:67 |
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| Enthalten in: |
EClinicalMedicine - 67(2024) vom: 24. Jan., Seite 102404 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Schoergenhofer, Christian [VerfasserIn] |
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| Themen: |
Journal Article |
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| Anmerkungen: |
Date Revised 28.01.2024 published: Electronic-eCollection ClinicalTrials.gov: NCT02814708 Citation Status PubMed-not-MEDLINE |
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| doi: |
10.1016/j.eclinm.2023.102404 |
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| 100 | 1 | |a Schoergenhofer, Christian |e verfasserin |4 aut | |
| 245 | 1 | 2 | |a A randomized, double-blind study on the safety and immunogenicity of rTSST-1 variant vaccine |b phase 2 results |
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| 500 | |a ClinicalTrials.gov: NCT02814708 | ||
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| 520 | |a © 2024 Published by Elsevier Ltd. | ||
| 520 | |a 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 | ||
| 520 | |a 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 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 | ||
| 520 | |a Findings: 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 | ||
| 520 | |a 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 | ||
| 520 | |a Funding: Biomedizinische Forschung & Bio-Produkte AG funded this study | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Staphylococcus aureus | |
| 650 | 4 | |a Superantigen | |
| 650 | 4 | |a TSST-1 | |
| 650 | 4 | |a Toxic shock syndrome | |
| 650 | 4 | |a Vaccine | |
| 700 | 1 | |a Gelbenegger, Georg |e verfasserin |4 aut | |
| 700 | 1 | |a Hasanacevic, Dzenita |e verfasserin |4 aut | |
| 700 | 1 | |a Schöner, Léa |e verfasserin |4 aut | |
| 700 | 1 | |a Steiner, Margarete M |e verfasserin |4 aut | |
| 700 | 1 | |a Firbas, Christa |e verfasserin |4 aut | |
| 700 | 1 | |a Buchtele, Nina |e verfasserin |4 aut | |
| 700 | 1 | |a Derhaschnig, Ulla |e verfasserin |4 aut | |
| 700 | 1 | |a Tanzmann, Andreas |e verfasserin |4 aut | |
| 700 | 1 | |a Model, Nina |e verfasserin |4 aut | |
| 700 | 1 | |a Larcher-Senn, Julian |e verfasserin |4 aut | |
| 700 | 1 | |a Drost, Manuel |e verfasserin |4 aut | |
| 700 | 1 | |a Eibl, Martha M |e verfasserin |4 aut | |
| 700 | 1 | |a Roetzer, Andreas |e verfasserin |4 aut | |
| 700 | 1 | |a Jilma, Bernd |e verfasserin |4 aut | |
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