PMID- 30414782 OWN - NLM STAT- MEDLINE DCOM- 20190422 LR - 20190422 IS - 1873-2518 (Electronic) IS - 0264-410X (Linking) VI - 36 IP - 50 DP - 2018 Nov 29 TI - Immunogenicity and safety of the 4CMenB and MenACWY-CRM meningococcal vaccines administered concomitantly in infants: A phase 3b, randomized controlled trial. PG - 7609-7617 LID - S0264-410X(18)31493-2 [pii] LID - 10.1016/j.vaccine.2018.10.096 [doi] AB - BACKGROUND: Invasive meningococcal disease has its highest incidence in infants. Co-administration of serogroup B (4CMenB) and quadrivalent conjugate (MenACWY-CRM) vaccines could protect against 5 clinically-relevant meningococcal serogroups. METHODS: This phase 3b, open, multicenter study (NCT02106390), conducted in Mexico and Argentina, enrolled and randomized (1:1:1) 750 healthy infants to receive either 4CMenB co-administered with MenACWY-CRM (4CMenB/MenACWY group), 4CMenB (4CMenB group), or MenACWY-CRM alone (MenACWY group) at ages 3, 5, 7 and 13 months. Non-inferiority of immune responses of co-administration to single administration of vaccines was assessed at 1 month post-booster dose (primary objective). Immunogenicity was evaluated pre- and 1 month post-primary and booster vaccinations using human serum bactericidal assay (hSBA). Safety was assessed. RESULTS: At 1 month post-booster vaccination, between-group hSBA geometric mean titer (GMT) ratios ranged from 0.89 to 1.03 for serogroup B strains (group 4CMenB/MenACWY over 4CMenB), and from 1.05 to 2.48 for ACWY serogroups (group 4CMenB/MenACWY over MenACWY). The lower limit of the 2-sided 95% confidence intervals for all GMT ratios was >0.5; the primary objective was demonstrated. Across all groups and serogroup B strains, 68-100% and 87-100% of children had hSBA titers >/=5 at 1 month post-primary and booster vaccination, respectively. For serogroups ACWY, >/=96% (post-primary vaccination) and >/=98% (post-booster vaccination) of children in all groups had hSBA titers >/=4. Post-booster vaccination, GMTs increased >/=5.99-fold from pre-booster values for each strain/serogroup. Solicited adverse events (AEs) were more frequent in groups 4CMenB/MenACWY and 4CMenB than in MenACWY; incidence of all other AEs was similar between groups. Serious AEs were reported for 6, 13, and 11 participants in groups 4CMenB/MenACWY, 4CMenB, and MenACWY, respectively; 1 (group 4CMenB) was considered vaccine-related. CONCLUSION: Immune responses elicited by co-administration of 4CMenB and MenACWY-CRM was non-inferior to single immunization. Co-administration of vaccines was immunogenic and well tolerated in infants. ClinicalTrials.gov: NCT02106390. CI - Copyright (c) 2018 GlaxoSmithKline Biologiclas SA. Published by Elsevier Ltd.. All rights reserved. FAU - Macias Parra, Mercedes AU - Macias Parra M AD - Instituto Nacional de Pediatria, Insurgentes Cuicuilco, 04530 Mexico City, Mexico. Electronic address: mermacpar@hotmail.com. FAU - Gentile, Angela AU - Gentile A AD - Hospital de Ninos "Ricardo Gutierrez", Gallo 1330, Ciudad Autonoma de Buenos Aires, Argentina. Electronic address: angelagentile@fibertel.com.ar. FAU - Vazquez Narvaez, Jorge Alejandro AU - Vazquez Narvaez JA AD - Asociacion de Investigacion Pediatrica Y Adultos (AINPAD A.C.), Montana Monarca No 31 Consultorio 209 y 2010 Col Jesus del Monte Morelia, Michoacan CP58350, Mexico. Electronic address: jorge.vazquez@ainpad.com.mx. FAU - Capdevila, Alejandro AU - Capdevila A AD - Paideia, Investigacion Clinica en Pediatria, Salguero 2835, Ciudad Autonoma de Buenos Aires, Argentina. Electronic address: vax_ar@yahoo.com. FAU - Minguez, Angel AU - Minguez A AD - Hospital Nuestra Senora de la Misericordia del Nuevo Siglo, Belgrano 1502, 5000 Cordoba, Argentina. Electronic address: angelminguez04@yahoo.com.ar. FAU - Carrascal, Monica AU - Carrascal M AD - CAIMED Investigacion en Salud S.A de C.V, Calle de Manzanillo # 100 Colonia Roma Sur, Piso 2 Delegacion Cuauhtemoc, Mexico City, Mexico. Electronic address: monica.carrascal@caimed.com. FAU - Willemsen, Arnold AU - Willemsen A AD - Plus100 B.V. c/o GSK, Hullenbergweg 83-85, 1101 CL Amsterdam, the Netherlands. Electronic address: arnold.x.willemsen@gsk.com. FAU - Bhusal, Chiranjiwi AU - Bhusal C AD - GSK, Via Fiorentina, 1, 53100 Siena, Italy. Electronic address: chiranjiwi.x.bhusal@gsk.com. FAU - Toneatto, Daniela AU - Toneatto D AD - GSK, Via Fiorentina, 1, 53100 Siena, Italy. Electronic address: daniela.x.toneatto@gsk.com. LA - eng PT - Clinical Trial, Phase III PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20181107 PL - Netherlands TA - Vaccine JT - Vaccine JID - 8406899 RN - 0 (4CMenB vaccine) RN - 0 (MenACWY) RN - 0 (Meningococcal Vaccines) RN - 0 (Vaccines, Conjugate) SB - IM MH - Argentina MH - Blood Bactericidal Activity MH - Drug-Related Side Effects and Adverse Reactions/epidemiology/pathology MH - Female MH - Healthy Volunteers MH - Humans MH - *Immunization Schedule MH - Incidence MH - Infant MH - Male MH - Meningitis, Meningococcal/prevention & control MH - Meningococcal Vaccines/administration & dosage/*adverse effects/*immunology MH - Mexico MH - Vaccines, Conjugate/administration & dosage/adverse effects/immunology OTO - NOTNLM OT - *4CMenB OT - *Co-administration OT - *Infants OT - *MenACWY-CRM OT - *Meningococcal vaccination EDAT- 2018/11/12 06:00 MHDA- 2019/04/23 06:00 CRDT- 2018/11/12 06:00 PHST- 2018/04/17 00:00 [received] PHST- 2018/10/28 00:00 [revised] PHST- 2018/10/30 00:00 [accepted] PHST- 2018/11/12 06:00 [pubmed] PHST- 2019/04/23 06:00 [medline] PHST- 2018/11/12 06:00 [entrez] AID - S0264-410X(18)31493-2 [pii] AID - 10.1016/j.vaccine.2018.10.096 [doi] PST - ppublish SO - Vaccine. 2018 Nov 29;36(50):7609-7617. doi: 10.1016/j.vaccine.2018.10.096. Epub 2018 Nov 7.