Immunogenicity and safety of concomitant administration of meningococcal serogroup B (4CMenB) and serogroup C (MenC-CRM) vaccines in infants: A phase 3b, randomized controlled trial.
After implementation of routine infant MenC vaccination, MenB remains a serious cause of meningococcal disease, yet to be targeted by vaccination programs in several countries. This study (NCT01339923) investigated the immunogenicity and safety of MenC CRM-conjugated vaccine (MenC-CRM) concomitantly administered with MenB vaccine (4CMenB).



Infants (N=251) were randomised 1:1 to receive 4CMenB and MenC-CRM (Group 1) or MenC-CRM alone (Group 2) at 3 and 5months (M3, M5) and a booster at 12months of age (M12), and pneumococcal vaccine at M3, M5, M7, M12. Antibody responses to meningococcal vaccines were measured at M3, M6, M12, and M13. Non-inferiority of MenC-CRM response in Group 1 vs Group 2 was demonstrated at M6 and M13, if the lower limit of the 95% confidence interval (LL95%CI) of the difference in percentage of infants with hSBA titres ≥1:8 was >-10%. Sufficiency of MenB response was achieved if LL95%CI of the percentage of infants with hSBA titres ≥1:4 against fHbp, NadA and PorA strains was ≥70% at M6 or ≥75% at M13. Adverse events (AEs) were collected for 7days post-vaccination, and serious AEs (SAEs) and medically attended AEs throughout the study.



Non-inferiority of MenC response in Group 1 vs Group 2 (LL95%CI -6.4% [M6]; -5.2% [M13]) and sufficiency of MenB response in Group 1 (LL95%CI 92%, 90%, 89% [M6]; 97%, 92%, 93% [M13] against fHbp, NadA, PorA, respectively) were demonstrated. Higher rates of mild to moderate solicited AEs were reported in Group 1. Unsolicited AEs and SAEs incidences were similar across groups.



Concomitant administration of MenC-CRM and 4CMenB in infants was immunogenic, resulting in non-inferior responses against MenC compared to MenC-CRM alone and demonstration of sufficient immune response to MenB, after primary and booster vaccination. Reactogenicity was higher for concomitant vaccines administration, but no safety concerns were identified.
Santa Casa de São Paulo School of Medical Sciences and CDEC, São Paulo, Brazil. Electronic address: masafadi@uol.com.br.
Marco Aurelio
MA
P Safadi
Hospital Clinico Universitario de Santiago de Compostela, Santiago de Compostela, Spain.
Federico
F
Martinon-Torres
CRIE UNIFESP, Universidade Federal de São Paulo, São Paulo, Brazil.
Lily Yin
LY
Weckx
CPEC - Associação Obras Sociais Irma Dulce and Oswaldo Cruz Foundation, Brazilian Ministry of Health, Salvador, Brazil.
Edson Duarte
ED
Moreira
Instituto de Medicina Integral Professor Fernando Figueira, Boa Vista Recife, PE, Brazil.
Eduardo Jorge
EJ
da Fonseca Lima
GSK, Amsterdam, The Netherlands.
Ilhem
I
Mensi
GSK, Siena, Italy.
Marco
M
Calabresi
GSK, Siena, Italy.
Daniela
D
Toneatto
D000907:Antibodies, Bacterial / Q000097:blood; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology / Q000473:pathology; D006801:Humans; D007115:Immunization Schedule; D007223:Infant; D022401:Meningococcal Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D013997:Time Factors; D016896:Treatment Outcome
C570015:4CMenB vaccine; D000907:Antibodies, Bacterial; C000625559:MenC-CRM vaccine; D022401:Meningococcal Vaccines
4CMenB; Immunogenicity; Infants; MenC-CRM; Safety