DAR-901 vaccine for the prevention of infection with Mycobacterium tuberculosis among BCG-immunized adolescents in Tanzania: A randomized controlled, double-blind phase 2b trial
| Autor: | Wendy Wieland-Alter, Robert D. Arbeit, Isaac Maro, Lisa V. Adams, Albert Magohe, Chris Bailey-Kellogg, Jamila Said, Susan Tvaroha, Christiaan A. Rees, Keiko Nakamura, Patricia Munseri, Mecky Matee, Todd A. MacKenzie, Maryam Amour, C. Robert Horsburgh, Kisali Pallangyo, C. Fordham von Reyn |
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| Rok vydání: | 2020 |
| Předmět: |
medicine.medical_specialty
Tuberculosis Adolescent 030231 tropical medicine Interferon gamma release assay Disease Placebo Tanzania Mycobacterium tuberculosis 03 medical and health sciences 0302 clinical medicine Immune system Internal medicine parasitic diseases medicine Humans 030212 general & internal medicine Abscess General Veterinary General Immunology and Microbiology biology Tuberculin Test business.industry Public Health Environmental and Occupational Health biology.organism_classification medicine.disease Infectious Diseases Cohort BCG Vaccine Molecular Medicine business Interferon-gamma Release Tests |
| Zdroj: | Vaccine. 38:7239-7245 |
| ISSN: | 0264-410X |
| Popis: | Background SRL172 prevented disease due to Mycobacterium tuberculosis in a Phase 3 trial. DAR-901 represents a scalable manufacturing process for SRL172. We sought to determine if DAR-901 would prevent infection with M. tuberculosis among BCG-primed adolescents age 13–15 years in Tanzania. Methods Adolescents with a negative T- SPOT.TBR interferon gamma release assay (IGRA) were randomized 1:1 to three intradermal injections of DAR-901 or saline placebo at 0, 2 and 4 months. Repeat IGRAs were performed at 2 months, and at 1, 2, and 3 years. The primary efficacy outcome was time to new TB infection (IGRA conversion to positive); the secondary outcome was time to persistent TB infection (IGRA conversion with repeat positive IGRA). Results Among 936 participants screened 667 were eligible and randomized to their first dose of vaccine or placebo (safety cohort). At 2 months, 625 participants remained IGRA-negative and were scheduled for the additional two doses (efficacy cohort). DAR-901 was safe and well-tolerated. One DAR-901 recipient developed a vaccine site abscess. Neither the primary nor secondary endpoints differed between the two treatment arms (p = 0.90 and p = 0.20, respectively). DAR-901 IGRA converters had median responses to ESAT-6 of 50.1 spot-forming cells (SFCs) vs. 19.6 SFCs in placebo IGRA converters (p = 0.03). Conclusions A three-dose series of 1 mg DAR-901 was safe and well-tolerated but did not prevent initial or persistent IGRA conversion. DAR-901 recipients with IGRA conversion demonstrated enhanced immune responses to ESAT-6. Since protection against disease may require different immunologic responses than protection against infection a trial of DAR-901 to prevent TB disease is warranted. Trial Registration. The trial is registered at ClinicalTrials.gov as NCT02712424. |
| Databáze: | OpenAIRE |
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