Immunogenicity and safety of a meningococcal a conjugate vaccine administered with routine EPI vaccines in African infants and toddlers.

In 2010, a Meningococcal group A (MenA) conjugate vaccine (PsA-TT) was WHO prequalified and introduced in preventive campaigns in 1-29 year-olds across the African Meningitis Belt. An extension of the indication to infants and toddlers in the Expanded Programme on Immunization (EPI) was pursued for the protection of new birth cohorts. Between 2008 and 2012, a Phase 2 randomized controlled trial was conducted in Ghana to assess the safety and immunogenicity of different PsA-TT formulations (10 μg, 5 μg or 2.5 μg of MenA polysaccharide) given as one or two doses with EPI vaccines at 14-18 weeks, 9-12 months, and 12-18 months of age (Study A). Between 2012 and 2013, a subsequent Phase 3 randomized controlled trial was conducted in Mali to assess the 10 μg and 5 μg formulations given as one or two doses with EPI vaccines at 9-12 and 15-18 months of age (Study B). Immunogenicity was assessed using a serum bactericidal antibody assay using rabbit complement (rSBA). Non-inferiority of the 5 μg and 2.5 μg PsA-TT formulations to the 10 μg formulation was demonstrated in Study A with ≥93 % seroconversion in MenA rSBA 28 days after each dose. Non-inferiority of the 5 μg to the 10 μg was demonstrated in Study B in terms of seroconversion in MenA rSBA at 28 days (≥97 %) when given as two doses at 9-12 and 15-18 months and as a single dose at 9-12 months. Non-inferiority with respect to most EPI antigens was demonstrated in pairwise comparisons across both studies. Adverse events and serious adverse events reported in either study following vaccinations were similar across vaccine groups. Results of both trials showed that the vaccine was safe and immunogenic when co-administered with the EPI, paving the way for a WHO recommendation for the 5 μg PsA-TT to be included in the EPI as a single dose at 9-18 months of age. PsA-TT-004, registered International Standard Randomized Controlled Trial Number: ISRCTN82484612; PsA-TT-007, International registration number: PACTR201110000328305.