Effect on meningococcal serogroup W immunogenicity when Tdap was administered prior, concurrent or subsequent to the quadrivalent (ACWY) meningococcal CRM197-conjugate vaccine in adult Hajj pilgrims: A randomised controlled trial

Abstract Immune responses to the capsular polysaccharide administered in the polysaccharide-protein conjugate vaccines can be either improved or suppressed by the pre-existence of immunity to the carrier protein. Receiving multiple vaccinations is essential for travellers such as Hajj pilgrims, and the use of conjugated vaccines is recommended. We studied the immune response to meningococcal serogroup W upon prior, concurrent and sequential administration of a quadrivalent meningococcal conjugate vaccine (MCV4) conjugated to CRM 197 (coadministered with 13 valent pneumococcal vaccine conjugate CRM 197 [PCV13]), and tetanus-diphtheria-acellular pertussis (Tdap) vaccine in Australian adults before attending the Hajj pilgrimage in 2014. Participants were randomly assigned, by computer-generated numbers, to three study arms by 1:1:1 ratio. Group A received Tdap followed by MCV4-CRM 197 (+PCV13) 3–4 weeks later. Group B received all three vaccines in a single visit. Group C received MCV4-CRM 197 (+PCV13) followed by Tdap 3–4 weeks later. Blood samples obtained prior to and 3–4 weeks after immunisation with MCV4-CRM 197 were tested for meningococcal serogroup W-specific serum bactericidal antibody responses using baby rabbit complement (rSBA). One hundred and seven participants aged between 18 and 64 (median 40) years completed the study. No significant difference in meningococcal serogroup W rSBA geometric mean titre (GMT) was observed between the study arms post vaccination with MCV-CRM 197 but Group A tended to have a slightly lower GMT (A = 404, B = 984 and C = 1235, p  = 0.15). No statistical difference was noticed between the groups in proportions of subjects achieving a ≥4-fold rise in rSBA titres or achieving rSBA titre ≥8 post vaccination. In conclusion, receipt of MCV4-CRM 197 vaccine prior, concurrent or subsequent to Tdap has similar immunologic response, and hence concurrent administration is both immunogenic and practical. However, further investigation into whether carrier induced suppression is a public health issue is suggested. Clinical trial registration: ANZCTR no. ACTRN12613000536763.