Over the last decades, different quadrivalent antimeningococcal vaccine formulations (diphteria toxoid conjugate, MenACWY-D; tetanus toxoid conjugate, MenACWY-TT; CRM197 protein conjugate, MenACWY-CRM) have been developed. However, their availability varies, both in terms of authorized formulations and of inclusion in vaccination schedules. Furthermore, several countries include only the monovalent meningococcal C (MenC) vaccine in their immunization programmes. Finally, there is currently no updated systematic review that directly compares the MenACWY formulations. Thus, we summarized the evidence on efficacy and safety through four parallel, independent systematic literature reviews with meta-analysis which included randomized controlled trials comparing the abovementioned vaccines. A total of 16 studies have been included. In terms of efficacy, MenACWY-TT outperformed MenACWY-D and MenACWY-CRM for A, W-135, and Y serogroups, while no significant difference was found for serogroup C. Furthermore, we did not find significant differences in efficacy between MenC and MenACWY-TT. Regarding the safety, we were able to perform a quantitative analysis only between MenACWY-TT and MenC, finding no significant differences. Similarly, among the different MenACWY formulations no relevant differences were identified. These findings suggest that MenACWY-TT could be preferable to other formulations to improve current vaccination programs and to better develop future immunization policies.

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