title: 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.
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).
  
  
  CONCLUSIONS
  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.affiliation: Medical Research Council Unit, The Gambia, PO Box 273, Banjul, Gambia. Electronic address: oidoko@mrc.gm.
authors.forename: Olubukola T
authors.initials: OT
authors.lastname: Idoko
authors.affiliation: Medical Research Council Unit, The Gambia, PO Box 273, Banjul, Gambia. Electronic address: oowolabi@mrc.gm.
authors.forename: Olumuyiwa A
authors.initials: OA
authors.lastname: Owolabi
authors.affiliation: Medical Research Council Unit, The Gambia, PO Box 273, Banjul, Gambia. Electronic address: powiafe@mrc.gm.
authors.forename: Patrick K
authors.initials: PK
authors.lastname: Owiafe
authors.affiliation: GlaxoSmithKline Vaccines, Rue de l'Institut 89, BE-1330 Rixensart, Belgium. Electronic address: philippe.moris@gsk.com.
authors.forename: Philippe
authors.initials: P
authors.lastname: Moris
authors.affiliation: Medical Research Council Unit, The Gambia, PO Box 273, Banjul, Gambia. Electronic address: aaodutola@mrc.gm.
authors.forename: Aderonke
authors.initials: A
authors.lastname: Odutola
authors.affiliation: GlaxoSmithKline Vaccines, Rue de l'Institut 89, BE-1330 Rixensart, Belgium. Electronic address: anne.g.bollaerts@gsk.com.
authors.forename: Anne
authors.initials: A
authors.lastname: Bollaerts
authors.affiliation: Medical Research Council Unit, The Gambia, PO Box 273, Banjul, Gambia. Electronic address: tundeyogundare@yahoo.com.
authors.forename: Ezra
authors.initials: E
authors.lastname: Ogundare
authors.affiliation: GlaxoSmithKline Vaccines, Rue de l'Institut 89, BE-1330 Rixensart, Belgium. Electronic address: erik.x.jongert@gsk.com.
authors.forename: Erik
authors.initials: E
authors.lastname: Jongert
authors.affiliation: GlaxoSmithKline Vaccines, Rue de l'Institut 89, BE-1330 Rixensart, Belgium. Electronic address: marie-ange.demoitie@gsk.com.
authors.forename: Marie-Ange
authors.initials: MA
authors.lastname: Demoitié
authors.affiliation: GlaxoSmithKline Vaccines, Rue de l'Institut 89, BE-1330 Rixensart, Belgium. Electronic address: opokua.ofori-anyinam@gsk.com.
authors.forename: Opokua
authors.initials: O
authors.lastname: Ofori-Anyinam
authors.affiliation: Medical Research Council Unit, The Gambia, PO Box 273, Banjul, Gambia; WHO Regional Office for Africa, Brazzaville, Congo. Electronic address: otama@who.int.
authors.forename: Martin O
authors.initials: MO
authors.lastname: Ota
mesh_terms: D000907:Antibodies, Bacterial / Q000096:biosynthesis; D001500:BCG Vaccine / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D004306:Dose-Response Relationship, Immunologic; D006801:Humans; D007111:Immunity, Cellular; D007115:Immunization Schedule; D007117:Immunization, Secondary / Q000009:adverse effects* / Q000379:methods; D007074:Immunoglobulin G / Q000096:biosynthesis; D007223:Infant; D014376:Tuberculosis / Q000517:prevention & control*; D032581:Tuberculosis Vaccines / Q000009:adverse effects* / Q000276:immunology*
chemical_list: D000907:Antibodies, Bacterial; D001500:BCG Vaccine; D016207:Cytokines; D007074:Immunoglobulin G; D032581:Tuberculosis Vaccines
keywords: AS01; Co-administration; EPI; M72; Tuberculosis vaccine