Safety and immunogenicity of four doses of Neisseria meningitidis group C vaccine conjugated to CRM197 in United States infants

Background. Following widespread use of conjugate pneumococcal vaccine, Nei sseria meningitidis likely will become the leading cause of bacterial sepsi s and meningitis in US children. This report describes the safety and immun ogenicity in US children of four consecutive doses of a meningococcal group C vaccine conjugated to CRM,,, via reductive amination (MnCC). Methods. One hundred six healthy a-month-old infants received MnCC at 2, 4 and 6 months of age in a randomized controlled double blind study; children in the other treatment arm were given a 7-valent conjugate pneumococcal va ccine. Parents reenrolled 64 of these children at 12 to 15 months to receiv e a fourth dose of MnCC. Routine childhood vaccines, including DTP, were co administered. Temperatures and symptoms were recorded for 3 days after each immunization. Serum enzyme-linked immunosorbent assay IgG and bactericidal antibodies were measured prevaccination and before and 1 month after Doses 3 and 4. Results. Moderate to severe local reactions, defined as erythema or indurat ion greater than or equal to2.4 cm or pain that interfered with limb moveme nt was reported after 6 to 3.2% of MnCC injections, depending on the reacti on and dose. Fever occurred in 23 to 37% of children, but the contribution of MnCC to the febrile reactions is unknown. Geometric mean concentrations of IgG antibody to group C meningococcal polysaccharide were 3.72 mug/ml af ter Dose 3 and 8.03 mug/ml after the booster. Geometric mean functional ser um bactericidal antibody titers after Doses 3 and 4 were 1:463 and 1:2341, respectively. One hundred percent of children had a serum bactericidal anti body titer of greater than or equal to1:64 after three doses and greater th an or equal to1:128 after the booster. Conclusions. The MnCC vaccine had an acceptable safety profile and generate d high titers of bactericidal antibody in immunized US infants and toddlers . It appears to be an attractive candidate vaccine for the prevention of se rogroup C meningococcal disease in young children.