Context Immunization with a meningococcal tetravalent ( serogroup ACWY) glycoconjugate vaccine is recommended for all US adolescents. However, the currently licensed vaccine is poorly immunogenic in infancy, when the highest rates of disease are observed. Objective To determine the immunogenicity of a novel tetravalent CRM197-conjugated meningococcal vaccine ( MenACWY) in infants. Design, Setting, and Participants Randomized, open- label, controlled study of 225 UK and 196 Canadian 2- month- olds from August 2004 to September 2006. Intervention UK infants received a primary course of MenACWY ( at 2, 3, and 4 months or 2 and 4 months) or Neisseria meningitidis serogroup C monovalent meningococcal glycoconjugate vaccine ( MenC) ( at 2 and 4 months). All received MenACWY at 12 months. Canadian infants received MenACWY at 2, 4, and 6 months or 2 and 4 months; at 12 months they received MenACWY, a plain tetravalent polysaccharide vaccine, or no vaccine. Main Outcome Measure Percentage of infants with a human complement serum bactericidal activity (hSBA) titer >= 1: 4 after a primary course of MenACWY and after a 12- month booster. Safety and reactogenicity of MenACWY were also assessed. Results According to the prespecified per- protocol analysis, the percentages ( 95% Cls) of MenACWY 2-, 3-, and 4- month recipients with hSBA titers >= 1: 4 after primary immunization were serogroup A, 93% ( 84%- 98%); C, 96% ( 89%- 99%); W- 135, 97% ( 90%- 100%); and Y, 94% ( 86%- 98%). With a post hoc intention- to- treat analysis with imputed values for missing data, these values were unchanged for serogroups C and Y; for serogroup A, values were 92% ( 84%- 97%), and for W- 135, 97% ( 91%- 99%). For the per- protocol analysis of MenACWY 2-, 4-, and 6- month recipients, the percentages ( 95% Cls) of responders were A, 81%( 71%- 89%); C, 98%( 92%- 100%); W- 135,99% ( 93%- 100%); and Y, 98% ( 92%- 100%). With the imputed value analysis, these values were A, 83% ( 74%- 89%); C, 98% ( 93%- 99%); W- 135, 99% ( 94%- 100%); and Y, 98% ( 92%- 99%). At least 84% of MenACWY 2- and 4- month recipients achieved hSBA titers >= 1: 4 for serogroups C, W- 135, and Y after primary immunization, as did at least 60% for serogroup A ( per- protocol and imputation analysis). At least 95% of primary and booster MenACWY recipients achieved hSBA titers >= 1: 4 for serogroups C, W- 135, and Y at 13 months, as did at least 84% for serogroup A ( per- protocol and imputation analysis). During the primary immunization course, postimmunization pain on leg movement was observed in 2% of UK Men ACWY 2- and 4- month recipients and4% of MenC 2- and 4- month recipients; a temperature of 38 C or greater was observed in 4% and 2% in these groups, respectively. Conclusion MenACWY is well tolerated and immunogenic in infancy. Trial Registration clinicaltrials. gov Identifier: NCT00262002.
