Olubukola T Idoko1, Olumuyiwa A Owolabi2, Patrick K Owiafe3, Philippe Moris4, Aderonke Odutola5, Anne Bollaerts6, Ezra Ogundare7, Erik Jongert8, Marie-Ange Demoitié9, Opokua Ofori-Anyinam10, Martin O Ota11. 1. Medical Research Council Unit, The Gambia, PO Box 273, Banjul, Gambia. Electronic address: oidoko@mrc.gm. 2. Medical Research Council Unit, The Gambia, PO Box 273, Banjul, Gambia. Electronic address: oowolabi@mrc.gm. 3. Medical Research Council Unit, The Gambia, PO Box 273, Banjul, Gambia. Electronic address: powiafe@mrc.gm. 4. GlaxoSmithKline Vaccines, Rue de l'Institut 89, BE-1330 Rixensart, Belgium. Electronic address: philippe.moris@gsk.com. 5. Medical Research Council Unit, The Gambia, PO Box 273, Banjul, Gambia. Electronic address: aaodutola@mrc.gm. 6. GlaxoSmithKline Vaccines, Rue de l'Institut 89, BE-1330 Rixensart, Belgium. Electronic address: anne.g.bollaerts@gsk.com. 7. Medical Research Council Unit, The Gambia, PO Box 273, Banjul, Gambia. Electronic address: tundeyogundare@yahoo.com. 8. GlaxoSmithKline Vaccines, Rue de l'Institut 89, BE-1330 Rixensart, Belgium. Electronic address: erik.x.jongert@gsk.com. 9. GlaxoSmithKline Vaccines, Rue de l'Institut 89, BE-1330 Rixensart, Belgium. Electronic address: marie-ange.demoitie@gsk.com. 10. GlaxoSmithKline Vaccines, Rue de l'Institut 89, BE-1330 Rixensart, Belgium. Electronic address: opokua.ofori-anyinam@gsk.com. 11. Medical Research Council Unit, The Gambia, PO Box 273, Banjul, Gambia; WHO Regional Office for Africa, Brazzaville, Congo. Electronic address: otama@who.int.
Abstract
UNLABELLED: 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.
UNLABELLED: 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.
Authors: Chelsea Carpenter; John Sidney; Ravi Kolla; Kaustuv Nayak; Helena Tomiyama; Claudia Tomiyama; Oscar A Padilla; Virginie Rozot; Syed F Ahamed; Carlos Ponte; Valeria Rolla; Paulo R Antas; Anmol Chandele; John Kenneth; Seetha Laxmi; Edward Makgotlho; Valentina Vanini; Giuseppe Ippolito; Alexandra S Kazanova; Alexander V Panteleev; Willem Hanekom; Harriet Mayanja-Kizza; David Lewinsohn; Mayuko Saito; M Juliana McElrath; W Henry Boom; Delia Goletti; Robert Gilman; Irina V Lyadova; Thomas J Scriba; Esper G Kallas; Kaja Murali-Krishna; Alessandro Sette; Cecilia S Lindestam Arlehamn Journal: Tuberculosis (Edinb) Date: 2015-08-01 Impact factor: 3.131