Safety and immunogenicity of 4CMenB and MenACWY-CRM meningococcal vaccines when administered concomitantly in healthy adolescents: A phase 3b, randomized, observer-blind study.

Abstract / Summary

Meningococcal vaccination of adolescents/young adults is recommended in various countries, including the United States (US). This phase 3b, observer-blind study (NCT04318548) evaluated the safety, reactogenicity, and immunogenicity of serogroup B vaccine, 4CMenB, and quadrivalent conjugate vaccine, MenACWY-CRM, when co-administered to healthy individuals aged 16-18 y, as per US Advisory Committee on Immunization Practices recommendations. Adolescents, who had received MenACWY vaccination ≥4 y previously, were randomized (N = 940; 1:1:1) to one of three groups to assess co-administration versus 4CMenB and MenACWY-CRM administered alone. Co-primary objectives were to demonstrate the non-inferiority of antibody responses after concomitant administration to antibody responses after 4CMenB (two doses administered 2 months apart) and MenACWY-CRM (single dose), as measured by human serum bactericidal assay (hSBA). Vaccine safety and reactogenicity were assessed as another primary objective. The co-primary endpoints were met: the lower limit of 2-sided 95% confidence intervals for all between-group ratios of hSBA geometric mean titers was >0.5 for the concomitant administration group versus 4CMenB group and MenACWY-CRM group. hSBA data after two 4CMenB doses and one MenACWY-CRM dose showed comparable between-group geometric mean ratios versus baseline, and percentages of participants with 4-fold rises in titers and titers ≥lower limit of quantitation. The safety profile of 4CMenB co-administered with MenACWY-CRM was comparable with that of 4CMenB administered alone. In conclusion, 4CMenB and MenACWY-CRM co-administration was well tolerated in adolescents aged 16-18 y and immune responses were comparable versus administration of each vaccine alone, which is consistent with a previous study of co-administration in infants. Invasive meningococcal disease, caused by the bacterium Neisseria meningitidis, poses a life-threatening risk but can be prevented through vaccination. Effective vaccines are available against the most common disease-causing meningococcal serogroups, A, B, C, W, and Y. Evidence from clinical studies and immunization programs over the last decade with the 4-component meningococcal serogroup B vaccine, 4CMenB, and serogroups A, C, W, and Y vaccine, MenACWY-CRM, confirms the effectiveness of both vaccines in population age groups at higher risk of meningococcal disease, including infants and adolescents. It was previously shown that the administration of 4CMenB and MenACWY-CRM to healthy infants at the same visit induced good immune responses and was well tolerated by young children. Adolescent vaccination with 4CMenB and MenACWY-CRM is recommended in various countries, including in the United States. We conducted a study to test the safety of concomitant administration and its ability to induce immune responses in 945 healthy adolescents aged 16–18 y; 834 from the United States and 111 from Italy. We found that most reactions to the 4CMenB and MenACWY-CRM injections were mild or moderate, and were similar whether the vaccines were given together or separately, with no unexpected side effects. Co-administration to adolescents induced robust immune responses against serogroup B and serogroups A, C, W, and Y. These results support the use of concomitant meningococcal vaccinations in adolescent immunization programs.

Related Clinical Guidelines