Randomized Trial on the Safety, Tolerability, and Immunogenicity of MenACWY-CRM, an Investigational Quadrivalent Meningococcal Glycoconjugate Vaccine, Administered Concomitantly with a Combined Tetanus, Reduced Diphtheria, and Acellular Pertussis Vaccine in Adolescents and Young Adults

Abstract

This study evaluated the safety, tolerability, and immunogenicity of an investigational quadrivalent meningococcal conjugate vaccine, MenACWY-CRM, when administered concomitantly with a combined tetanus, reduced diphtheria, and acellular pertussis (Tdap) vaccine, in subjects aged 11 to 25 years. Subjects received either MenACWY-CRM and Tdap, MenACWY-CRM and saline placebo, or Tdap and saline placebo. No significant increase in reactogenicity and no clinically significant vaccine-related adverse events (AEs) occurred when MenACWY-CRM and Tdap were administered concomitantly. Similar immunogenic responses to diphtheria, tetanus, and meningococcal (serogroups A, C, W-135, and Y) antigens were observed, regardless of concomitant vaccine administration. Antipertussis antibody responses were comparable between vaccine groups for filamentous hemagglutinin and were slightly lower, although not clinically significantly, for pertussis toxoid and pertactin when the two vaccines were administered concomitantly. These results indicate that the investigational MenACWY-CRM vaccine is well tolerated and immunogenic and that it can be coadministered with Tdap to adolescents and young adults.

Immunogenicity and safety of a CRM-conjugated meningococcal ACWY vaccine administered concomitantly with routine vaccines starting at 2 months of age

“…11 MenACWY-CRM (Menveo ® , Novartis Vaccines and Diagnostics) is a quadrivalent (A, C, W-135, and Y) meningococcal vaccine conjugated to CRM 197 , a nontoxic mutant of diphtheria toxin, as the carrier protein. 12 Previous phase 2 and 3 studies demonstrated that MenACWY-CRM elicited highly immunogenic responses and was well-tolerated in adults, [13][14][15] adolescents, 13,16,17 children, 18,19 and importantly, young infants. Background: Infants are at the highest risk for meningococcal disease and a broadly protective and safe vaccine is an unmet need in this youngest population.…”

Immunogenicity and Safety of Combined Tetanus, Reduced Diphtheria, Acellular Pertussis Vaccine when Co-Administered with Quadrivalent Meningococcal Conjugate and Human Papillomavirus Vaccines in Healthy Adolescents

“…In contrast to previous studies examining co-administration of MenACWY-CRM and Tdap [16,17], non-inferiority criteria were met for all three pertussis antigens tested.…”

“…In the earlier studies, the direct comparators for Tdap immune responses were either Tdap alone [17] or Tdap administered with a placebo [16]. In contrast, the direct comparator group of the present study received a placebo with both Tdap and HPV4.…”

“…Moreover, concomitant administration of MenACWY-CRM did not decrease protective antibody responses to diphtheria, tetanus, or HPV. While the responses to the pertussis antigens did not meet the predefined non-inferiority criteria in the referenced studies [16,17], these findings are of unknown clinical significance, given the lack of an established serocorrelate of protection against pertussis disease. Neither of these studies included the comparison that is most relevant to current US adolescent recommendations: namely, the comparison of co-administration of MenACWY-CRM, Tdap, and HPV vaccines versus co-administration of Tdap and HPV vaccines alone.…”

“…Previous evaluations of concomitant administration of MenACWY-CRM with either Tdap alone [16] or with both Tdap and HPV vaccines [17] in healthy adolescents demonstrate that MenACWY-CRM is well tolerated and immunogenic against meningococcal serogroups A, C, W-135, and Y following co-administration. Moreover, concomitant administration of MenACWY-CRM did not decrease protective antibody responses to diphtheria, tetanus, or HPV.…”