Ten-year follow-up on efficacy, immunogenicity and safety of two doses of a combined measles-mumps-rubella-varicella vaccine or one dose of monovalent varicella vaccine: Results from five East European countries.


Journal

Vaccine
ISSN: 1873-2518
Titre abrégé: Vaccine
Pays: Netherlands
ID NLM: 8406899

Informations de publication

Date de publication:
06 05 2021
Historique:
received: 22 09 2020
revised: 17 02 2021
accepted: 26 03 2021
pubmed: 17 4 2021
medline: 25 5 2021
entrez: 16 4 2021
Statut: ppublish

Résumé

We assessed the 10-year efficacy, immunogenicity and safety of two doses of a combined measles-mumps-rubella-varicella vaccine (MMRV) or one dose of a monovalent varicella vaccine (V) in children from Czech Republic, Lithuania, Poland, Romania and Slovakia. This was a phase IIIB follow-up of an observer-blind, randomized, controlled trial (NCT00226499). In phase A, healthy children aged 12-22 months from 10 European countries were randomized in a 3:3:1 ratio to receive two doses of MMRV (MMRV group), one dose of MMR followed by one dose of V (MMR + V group), or two doses of MMR (MMR; control group), 42 days apart. Vaccine efficacy (VE) against varicella (confirmed by viral DNA detection or epidemiological link and clinical assessment) was calculated with 95% confidence intervals using Cox proportional hazards regression model. Immunogenicity was assessed as seropositivity rates and geometric mean concentrations (GMCs). Solicited and unsolicited adverse events (AEs) and serious AEs (SAEs) were recorded. A total of 3705 children were vaccinated (1590, MMRV group; 1586, MMR + V group; 529, MMR group). There were 663 confirmed varicella cases (47, MMRV group; 349, MMR + V group; 267, MMR group). VE ranged between 95.4% (Lithuania) and 97.4% (Slovakia) in the MMRV group and between 59.3% (Lithuania) and 74% (Slovakia) in the MMR + V group. At year 10, seropositivity rates were 99.5%-100% in the MMRV group, 98%-100% in the MMR + V group and 50%-100% in the MMR control group, and the anti-VZV antibody GMCs were comparable between MMRV and MMR + V groups. The occurrence of solicited and unsolicited AEs was similar across groups and no SAE was considered as vaccination-related. No new safety concerns were identified. Our results indicated that two doses of varicella zoster virus-containing vaccine provided better protection than one dose against varicella and induced antibody responses that persisted 10 years post-vaccination.

Sections du résumé

BACKGROUND
We assessed the 10-year efficacy, immunogenicity and safety of two doses of a combined measles-mumps-rubella-varicella vaccine (MMRV) or one dose of a monovalent varicella vaccine (V) in children from Czech Republic, Lithuania, Poland, Romania and Slovakia.
METHODS
This was a phase IIIB follow-up of an observer-blind, randomized, controlled trial (NCT00226499). In phase A, healthy children aged 12-22 months from 10 European countries were randomized in a 3:3:1 ratio to receive two doses of MMRV (MMRV group), one dose of MMR followed by one dose of V (MMR + V group), or two doses of MMR (MMR; control group), 42 days apart. Vaccine efficacy (VE) against varicella (confirmed by viral DNA detection or epidemiological link and clinical assessment) was calculated with 95% confidence intervals using Cox proportional hazards regression model. Immunogenicity was assessed as seropositivity rates and geometric mean concentrations (GMCs). Solicited and unsolicited adverse events (AEs) and serious AEs (SAEs) were recorded.
RESULTS
A total of 3705 children were vaccinated (1590, MMRV group; 1586, MMR + V group; 529, MMR group). There were 663 confirmed varicella cases (47, MMRV group; 349, MMR + V group; 267, MMR group). VE ranged between 95.4% (Lithuania) and 97.4% (Slovakia) in the MMRV group and between 59.3% (Lithuania) and 74% (Slovakia) in the MMR + V group. At year 10, seropositivity rates were 99.5%-100% in the MMRV group, 98%-100% in the MMR + V group and 50%-100% in the MMR control group, and the anti-VZV antibody GMCs were comparable between MMRV and MMR + V groups. The occurrence of solicited and unsolicited AEs was similar across groups and no SAE was considered as vaccination-related. No new safety concerns were identified.
CONCLUSIONS
Our results indicated that two doses of varicella zoster virus-containing vaccine provided better protection than one dose against varicella and induced antibody responses that persisted 10 years post-vaccination.

Identifiants

pubmed: 33858718
pii: S0264-410X(21)00401-1
doi: 10.1016/j.vaccine.2021.03.085
pii:
doi:

Substances chimiques

Antibodies, Viral 0
Chickenpox Vaccine 0
Measles-Mumps-Rubella Vaccine 0
Vaccines, Combined 0

Types de publication

Clinical Trial, Phase III Journal Article Randomized Controlled Trial Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

2643-2651

Informations de copyright

Copyright © 2021 GlaxoSmithKline Biologicals SA. Published by Elsevier Ltd.. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of Competing Interest GC, MAH, MP are employees of the GSK group of companies, and GC and MAH hold shares in the GSK group of companies as part of the employee remuneration. DV, JW, MS, RP, VU have received grants from the GSK group of companies during the conduct of the study. JW, MS have received consulting and lecture fees from the GSK group of companies. MS has received non-financial support from the GSK group of companies to attend scientific meetings, outside the submitted work. DV reports to have received personal fees by Biovomed during the conduct of the study. DV moreover reports to have received personal fees from the GSK group of companies, MSD, Sanofi and Pfizer, outside the submitted work. RR reports that her institution received fees during the conduct of the study. DP, GL, HCa, HCz, JB, NM, PP, RC, SM have not received any consulting fees and declare that they have no conflicts of interest and have no non-financial interest to declare.

Auteurs

Roman Prymula (R)

Charles University, Faculty of Medicine, Hradec Kralove, Czech Republic. Electronic address: Prymula@seznam.cz.

Michael Povey (M)

GSK, Wavre, Belgium. Electronic address: michael.x.povey@gsk.com.

Jerzy Brzostek (J)

Poradnia Chorob Zakaznych ZOZ Debica, Debica, Poland. Electronic address: jerzy_br@poczta.onet.pl.

Hana Cabrnochova (H)

Paediatric Centre, Prague, Czech Republic. Electronic address: hana@cabrnoch.cz.

Roman Chlibek (R)

University of Defence, Faculty of Military Health Sciences, Hradec Kralove, Czech Republic. Electronic address: roman.chlibek@unob.cz.

Hanna Czajka (H)

Faculty of Medicine, University of Rzeszow, Rzeszow, Poland and Infectious Diseases Outpatient Clinic, The St. Louis Regional Specialised Children's Hospital, Krakow, Poland. Electronic address: hanna.czajka@onet.pl.

Giedra Leviniene (G)

Pediatric Clinic, Lithuanian University of Health Sciences, Kaunas, Lithuania.

Sorin Man (S)

University of Medicine and Pharmacy "Iuliu Hatieganu", Cluj-Napoca, Romania.

Mihai Neamtu (M)

Lucian Blaga University of Sibiu, Faculty of Medicine, Sibiu, Romania. Electronic address: mihai.neamtu@ulbsibiu.ro.

Petr Pazdiora (P)

Department of Epidemiology, Medical Faculty Pilsen of Charles University, Czech Republic. Electronic address: PAZDIORA@fnplzen.cz.

Doina Plesca (D)

Pediatrics, University of Medicine and Pharmacy "Carol Davila", Bucharest, Romania.

Renata Ruzkova (R)

Pediatric Office Dr. Renata Ruzkova, Prague, Czech Republic. Electronic address: drruzkova@email.cz.

Maria Stefkovicova (M)

Faculty of Health Care, Alexander Dubcek University of Trencín, Trencín, Slovakia.

Vytautas Usonis (V)

Clinic of Children's Diseases, Institute of Clinical Medicine, Faculty of Medicine, Vilnius University, Vilnius, Lithuania. Electronic address: vytautas.usonis@mf.vu.lt.

Daniela Verdanova (D)

Nemocnice s ambulantni casti, Jindrichuv Hradec, Czech Republic. Electronic address: daniela.verdanova@seznam.cz.

Jacek Wysocki (J)

University of Medical Sciences, Poznan, Poland. Electronic address: jwysocki@ump.edu.pl.

Giacomo Casabona (G)

GSK, Wavre, Belgium. Electronic address: GIACOMO.X.CASABONA@GSK.COM.

Md Ahsan Habib (MA)

GSK, Wavre, Belgium. Electronic address: AHSAN.M.HABIB@GSK.COM.

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Classifications MeSH