Safety and immunogenicity of the M72/AS01 candidate tuberculosis vaccine when given as a booster to BCG in Gambian infants: an open-label randomized controlled trial
Olubukola T Idoko, Olumuyiwa A Owolabi, Patrick K Owiafe, Philippe Moris, Aderonke Odutola, Anne Bollaerts, Ezra Ogundare, Erik Jongert, Marie-Ange Demoitié, Opokua Ofori-Anyinam, Martin O Ota, Olubukola T Idoko, Olumuyiwa A Owolabi, Patrick K Owiafe, Philippe Moris, Aderonke Odutola, Anne Bollaerts, Ezra Ogundare, Erik Jongert, Marie-Ange Demoitié, Opokua Ofori-Anyinam, Martin O Ota
Abstract
We evaluated the candidate tuberculosis vaccine M72/AS01 in Bacille-Calmette-Guérin (BCG)-vaccinated infants after or concomitantly with Expanded-Programme-on-Immunization (EPI) vaccines.
Methods: In a Phase-II study in The Gambia (NCT01098474), 2 cohorts of 150 BCG-vaccinated infants each were randomized 1:1:1. The 'Outside-EPI' cohort received one or two M72/AS01 doses, or meningitis vaccine, 1-2 months after primary EPI vaccination. The 'Within-EPI' cohort received one or two M72/AS01 doses concomitantly with the third or last two doses of their primary EPI-regimen, respectively, or EPI vaccines alone. Safety, M72-specific humoral (ELISA) and cell-mediated (whole-blood ICS) responses, and humoral responses to EPI vaccines were assessed.
Results: M72/AS01 was acceptably tolerated with no vaccine-related serious adverse events reported. Seropositivity/seroprotection rates against EPI antigens in the Within-EPI cohort were comparable between groups, irrespective of M72/AS01 co-administration. Up to one year post M72/AS01 vaccination, M72-specific humoral and CD4(+) T-cell responses were higher after 2 doses versus 1 dose in both cohorts (p < 0.0001), and comparable between cohorts after either 1 or 2 doses (p > 0.05).
Conclusion: M72/AS01 given to infants after or concomitantly with EPI vaccines had an acceptable safety profile. Our results suggest no interference of immunogenicity profiles occurred following co-administration of M72/AS01 and EPI vaccines. Two M72/AS01 doses elicited higher immune responses than one dose.
Keywords: AS01; Co-administration; EPI; M72; Tuberculosis vaccine.
Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.
Source: PubMed