title: The immunogenicity and safety of a tetravalent measles-mumps-rubella-varicella vaccine when co-administered with conjugated meningococcal C vaccine to healthy children: A phase IIIb, randomized, multi-center study in Italy.
abstract: Multiple vaccination visits and administrations can be stressful for infants, parents and healthcare providers. Multivalent combination vaccines can deliver the required number of antigens in fewer injections and clinic visits, while vaccine co-administration can also reduce the number of visits. This non-inferiority study was undertaken to evaluate the feasibility of co-administering a combined measles-mumps-rubella-varicella (MMRV) vaccine with conjugated meningococcal C (MenC) vaccine in a large cohort of healthy Italian toddlers.
  
  
  
  Healthy subjects aged 13-15months were randomized (2:1:1) to receive single doses of either: co-administered MMRV+MenC at the same visit (MMRV+MenC group); or MMRV followed 42days later by MenC (MMRV group); or MenC followed 42days later by MMRV (MenC group). Blood samples were collected before and 43days after vaccination. Antibody titers against MMRV were measured using ELISA. Functional-anti-meningococcal-serogroup activity (rSBAMenC) was assessed using a serum bactericidal test. Solicited local and general reactions were recorded for up to 4 and 42days post-vaccination, respectively. Non-inferiority of MMRV+MenC to MMRV (post-dose-1 seroconversion rates) and MMRV+MenC to MenC (post-dose-1 seroprotection rates) was achieved if the lower limit (LL) of the 95% confidence interval (CI) for the group difference was ⩾-10% for each antigen.
  
  
  
  716 subjects were enrolled in the study. At 42days post-vaccination, the MMRV seroconversion rates were 99.3% (measles), 94.5% (mumps), 100% (rubella) and 99.7% (varicella) in the MMRV+MenC group, and 99.4%, 93.2%, 100% and 100%, respectively, in the MMRV group. The seroprotection rates against rSBA-MenC were 98.3% in the MMRV+MenC group and 99.3% in the MenC group. Non-inferiority was reached for all the vaccine antigens. The safety profiles were as expected for these vaccines.
  
  
  
  The immune responses elicited by co-administered MMRV+MenC were non-inferior to those elicited by MMRV or MenC alone and support vaccination of children with both vaccines at a single visit.
  
  
  
  NCT01506193.
authors.affiliation: Department of Health Sciences, School of Medical and Pharmaceutical Sciences, University of Genoa and IRCCS AOU San Martino - IST, L.go R. Benzi, 10 (Building 3), Genoa 16132, Italy. Electronic address: durando@unige.it.
authors.forename: Paolo
authors.initials: P
authors.lastname: Durando
authors.affiliation: Pediatric Highly Intensive Care Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan 20122, Italy. Electronic address: susanna.esposito@unimi.it.
authors.forename: Susanna
authors.initials: S
authors.lastname: Esposito
authors.affiliation: Corso Mazzini, 18, Clinica di Pediatria, Azienda Ospedaliera Maggiore della Carità, Piemonte, Novara 28100, Italy. Electronic address: gianni.bona@maggioreosp.novara.it.
authors.forename: Gianni
authors.initials: G
authors.lastname: Bona
authors.affiliation: Settore Igiene Pubblica, Corso Italia, 234, Servizio di Epidemiologia e Prevenzione, ASP di Catania, Sicilia, Catania 95129, Italy. Electronic address: mario.cuccia@aspct.it.
authors.forename: Mario
authors.initials: M
authors.lastname: Cuccia
authors.affiliation: Via Rizzeddu, 21, Servizio di Igiene Pubblica, Azienda Unità Sanitaria Locale n. 1 di Sassari, Sardegna, Sassari 07100, Italy. Electronic address: madesole@aslsassari.it.
authors.forename: Maria Giuseppina
authors.initials: MG
authors.lastname: Desole
authors.affiliation: Centro Servizi, Via Aldo Licitra, 11, Dipartimento di Prevenzione e Igiene Pubblica, ASP di Ragusa, Sicilia, Ragusa, RG 97100, Italy. Electronic address: servizio.epidemiologia@asp.rg.it.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Ferrera
authors.affiliation: Via Fossato di Mortara 64b, Dip. Scienze Mediche, Università degli Studi di Ferrara, Ferrara, Italy. Electronic address: giovanni.gabutti@unife.it.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Gabutti
authors.affiliation: Corso Francia, 10, Servizio di Igiene e Sanità Pubblica, ASL CN1, Piemonte, Cuneo 12100, Italy. Electronic address: angelo.pellegrino@aslcn1.it.
authors.forename: Angelo
authors.initials: A
authors.lastname: Pellegrino
authors.affiliation: Via Antonio di Rudinì, 8, Clinica Pediatrica Università di Milano, ASST Santi Paolo e Carlo, Lombardia, Milano 20142, Italy. Electronic address: filippo.salvini@asst-santipaolocarlo.it.
authors.forename: Filippo
authors.initials: F
authors.lastname: Salvini
authors.affiliation: GSK Vaccines, Philadelphia, United States. Electronic address: ouzama.n.henry@gsk.com.
authors.forename: Ouzama
authors.initials: O
authors.lastname: Henry
authors.affiliation: GSK Vaccines, Avenue Fleming 20, 1300 Wavre, Belgium. Electronic address: michael.x.povey@gsk.com.
authors.forename: Michael
authors.initials: M
authors.lastname: Povey
authors.affiliation: GSK Vaccines, Via A. Fleming 2, 37135 Verona, Italy. Electronic address: federico.e.marchetti@gsk.com.
authors.forename: Federico
authors.initials: F
authors.lastname: Marchetti
mesh_terms: D000914:Antibodies, Viral / Q000097:blood*; D019433:Chickenpox Vaccine / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005334:Fever; D064368:Healthy Volunteers; D014645:Herpesvirus 3, Human / Q000276:immunology; D006801:Humans; D007115:Immunization Schedule; D000071497:Immunogenicity, Vaccine; D007223:Infant; D007558:Italy; D008297:Male; D008459:Measles virus / Q000276:immunology; D022542:Measles-Mumps-Rubella Vaccine / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D008589:Meningococcal Infections / Q000517:prevention & control; D022401:Meningococcal Vaccines / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology; D009109:Mumps virus / Q000276:immunology; D012412:Rubella virus / Q000276:immunology; D000069078:Seroconversion; D017778:Vaccines, Combined / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology
chemical_list: D000914:Antibodies, Viral; D019433:Chickenpox Vaccine; D022542:Measles-Mumps-Rubella Vaccine; D022401:Meningococcal Vaccines; D017778:Vaccines, Combined; C050102:measles, mumps, rubella, varicella vaccine; C410218:serogroup C meningococcal conjugate vaccine
keywords: Conjugated meningococcal C vaccine; Immunogenicity; Italy; Measles-mumps-rubella-varicella vaccine; Safety; Vaccination schedule