A multivalent conjugate vaccine for prevention of meningococcal disease in infants.

AJOR PROGRESS HAS BEEN MADE IN THE DEVEL- opmentofmeningococcalvaccinesinthepast few years. Monovalent serogroup C conju- gate vaccines, shown to be immunogenic and effective in infants, have dramatically decreased the inci- dence of serogroup C disease in the countries in which they havebeenused. 1-4 Thisreductionhasoccurredamongthose immunized and, through a decrease in pharyngeal carriage of serogroup C Neisseria meningitidis, also among the un- immunizedpopulation. 5,6 Thesevaccinesdonotcoversero- group Y strains, an important cause of meningococcal dis- ease across all age groups in the United States, including infants, and are not licensed in the United States. A new tet- ravalent (serogroups A, C, W-135, and Y) conjugate vac- cine licensed for 2- to 55-year-olds is now recommended for all US adolescents, as well as other high-risk groups. 7 This recommendation was based on the fact that US ado- lescents were found to have both a relatively high inci- denceofmeningococcaldiseaseandahighcasefatalityrate. 7,8 monthsofage)anda2-doseschedule(2and4months)given along with the other vaccines in the routine immunization schedule of the respective countries. An additional group receivedtheserogroupCconjugatevaccineat2and4months ofage.At12monthsofage,somechildrenreceivedabooster dose of the study vaccine, some received a reduced dose of tetravalent polysaccharide vaccine as a probe for immuno- logic memory, and some received no additional meningo- coccal vaccine. The strengths of the study include assess- ments of multiple immunization schedules, a booster dose at 12 months of age, and immunologic memory. The primary objective of this study was to determine the proportion of children receiving 1 of the 3 primary dose schedules who had a human complement serum bacteri- cidal antibody (hSBA) titer of 1:4 or greater against each of the meningococcal serogroups included in the vaccine 1 month after the primary series. In general, an hSBA titer of 1:4 or greater is considered to be protective, although there is evidence that this assay underestimates protective immu- nity. A key finding was that at least 92% of infants who re- ceived the 2-, 3-, 4-month schedule had an hSBA titer of 1:4 orgreatertoall4serogroups.Forthe2-,4-,6-monthsched- ule, similar results were obtained for serogroups C, W-135, and Y, but the proportion of infants with an hSBA titer of at least 1:4 against serogroup A was lower at 81%. Inthe2-,4-monthprimaryseriesgroups,atleast84%had protectiveantibodylevelsto3ofthe4serogroups,with60% to 66% of infants having a protective titer against sero- group A. Following a booster dose at 12 months, at least 95% of infants developed a protective antibody level to 3 of the 4 serogroups, and 84% for serogroup A. The results for study participants who received immune challenge with a reduced dose of plain polysaccharide vaccine at 12 months, when compared with historical controls, suggest that the study vaccines induced immunologic memory, a key prop- erty of conjugate vaccines. Administration of the study vac- cine did not appear to adversely affect the immunogenicity oftheconcomitantlygivenpediatricvaccines.Moreover,re- actogenicity was similar to what would be expected for a conjugatevaccineand,amongchildrenwhoreceived2doses