These results confirm that MenACWY-CRM is well tolerated and immunogenic when administered to adults 19 to 55 years of age. The primary end point in the larger adolescent arm of this study was a lot-to-lot comparison, which confirmed that there were no differences in immunogenicity or reactogenicity profiles between lots (8
). This result permitted the comparison of the combined MenACWY-CRM lots with Menactra in both age groups. The rates of local reactions were slightly higher in the MenACWY-CRM group, and in contrast, the rates of systemic reactions were slightly higher in the Menactra group. Overall, both MenACWY-CRM and Menactra were well tolerated, with similar reactogenicity profiles, and no unexpected or otherwise clinically significant AEs related to the vaccines administered were reported in this study.
Following vaccination with MenACWY-CRM, the immune response, measured by hSBA GMT and seroresponse and highlighted in the reverse cumulative distribution curves (Fig. ), was statistically superior for serogroups C, W-135, and Y in comparison to the immune response of Menactra. Using the proportion of subjects with a postvaccination hSBA titer of ≥1:8, noninferiority of MenACWY-CRM to Menactra was demonstrated for all four serogroups, and statistical superiority criteria were met for serogroups C and Y. These results are similar to those reported for adolescents in this study (9
), in which the immune response to MenACWY-CRM, measured by hSBA GMT, was greater for all serogroups. However, in this study, subtle differences were noted in the immune response to serogroups A and C in the two age groups. In the adolescent group, statistical superiority criteria were met for all serogroups when using GMTs as the end point and for serogroups C, W-135, and Y when seroresponse and the proportion of subjects with a postvaccination hSBA titer of ≥1:8 were used as the end points. In comparison, statistical superiority criteria were not met for serogroup A using any end point. The reason for this difference between the two age groups is not clear.
While the clinical relevance of these higher hSBA GMT immune responses is difficult to assess, these results nonetheless suggest that the efficacy of MenACWY-CRM should be at least comparable to that of Menactra. Furthermore, the long-term persistence of the hSBA titers to the four vaccine serogroups following MenACWY-CRM vaccination is currently unknown, although studies to assess the persistence of the immune response following vaccination with MenACWY-CRM in various age groups are either ongoing or planned.
Immune response differences between MenACWY-CRM and Menactra may be related to differences in the carrier proteins used in each vaccine, namely, CRM197
and diphtheria toxoid, respectively. As CRM197
is a nontoxic mutant of the diphtheria toxin, it does not require detoxification using formaldehyde or glutaraldehyde, a process employed in the preparation of diphtheria toxoids that can cause extensive cross-linking of the carrier protein to accessory antigens, with significant epitope modification (3
). Additional features of the vaccine-manufacturing process for MenACWY-CRM that may contribute to these differences in immune responses include the techniques for producing oligosaccharides within a prespecified size range, the chemical linker used in the conjugation process, and the selective conjugation chemistry. These enable the generation of a consistent, reproducible, and well-characterized vaccine product with MenACWY-CRM (1
Due to the dynamic and varied nature of global meningococcal disease epidemiology, protection against as many serogroups as possible is desirable, particularly for high-risk groups, such as infants and adolescents. Vaccination is also important in populations such as young adults (notably, matriculating college students), military personnel, people with asplenia or terminal complement deficiencies, and travelers to or people residing in areas where meningococcal disease is endemic. Currently, the U.S. Advisory Committee on Immunization Practices (ACIP) recommends vaccination with a quadrivalent meningococcal polysaccharide protein conjugate vaccine for these groups (2
). However, there are no general recommendations for children and adolescents in most European countries, due to the relatively low incidence of vaccine-preventable meningococcal disease, apart from that caused by serogroup C. Broad meningococcal protection has particular relevance for adults, given that the serogroup distribution of meningococcal disease shifts with age, with serogroup Y contributing disproportionately in older age groups (6
). Recent data show serogroup Y to be responsible for approximately 44% of cases of meningococcal disease in individuals ≥18 years of age in the United States, compared with 18% in individuals ≤18 years of age (http://www.cdc.gov/ncidod/dbmd/abcs/survreports/mening07.pdf
), and the incidence of serogroup Y is also increasing in countries such as Colombia (7
In summary, the results of this study show that MenACWY-CRM is well tolerated and highly immunogenic, with a robust immunogenicity profile that compares favorably with that of the currently licensed diphtheria toxoid protein conjugate vaccine. These results build upon previous studies demonstrating the safety and immunogenicity of MenACWY-CRM across a full spectrum of age ranges (9
; Black et al., submitted) and suggest that this vaccine has the potential to be a highly effective tool to help prevent invasive meningococcal disease caused by serogroups A, C, W-135, and Y in populations at risk.