Protective activity of group C anticapsular antibodies elicited in two-year-olds by an investigational quadrivalent Neisseria meningitidis-diphtheria toxoid conjugate vaccine

Background: Quadrivalent capsular group A, C, Y and W-135 meningococcal conjugate (MC-4) vaccines are under development Objective: Predict efficacy of an investigational MC-4 vaccine in 2-year-old children for prevention of group C disease. Design: Measurement of group C antibody concentrations, avidity and bactericidal and passive protective activity in sera from 2-year-olds given I dose of MC-4 vaccine (N = 30) and 3-year-olds (N 30) and adults (N = 26) given 1 dose of meningococcal polysaccharide (MPS-4) vaccine. Results: One month after vaccination, the geometric mean anticapsular antibody concentration of children given MC-4 vaccine (3.1 mug/ml) was lower than that of control children (5.1 mug/ml; P < 0.04) or adults immunized with MPS-4 vaccine (22.9 mug/ml; P < 0.001). However, the percent of sera with protective bactericidal titers of greater than or equal to1/4 was higher in children given MC-4 vaccine (50%, versus 17% in children given MPS-4 vaccine; P < 0.02) and was not significantly different from that of immunized adults (65%). In children, the mean antibody avidity at I month was higher in the MC-4 group (22 nM(-1) versus 16 nM(-1) in the MPS-4 group; P = 0.002), and at 6 months increased in the MC-4 group (28 nM(-1); P < 0.001), but not in the MPS-4 vaccine group (17 nM(-1)). Higher avidity antibody gave greater passive protection in the infant rat bacteremia model than did lower avidity antibody (P < 0.03). Conclusions: Although MPS-4 vaccine elicited higher group C serum antibody concentrations in 3-year-olds than did MC-4 vaccine in 2-year-olds, the higher antibody avidity after MC-4 vaccine resulted in higher bactericidal and passive protective activity.