Immunogenicity and safety of combined measles-mumps-rubella-varicella vaccine using new measles and rubella working seeds in healthy children in Taiwan and Singapore

Abstract

Aim: This study evaluated the immunogenicity and safety of tetravalent measles-mumps-rubella-varicella (MMRV) vaccine produced with measles and rubella monovalent bulks derived from a newly established working seed virus stock (MMRV_{new WS}) compared with the combined MMRV vaccine derived from the current seed virus stock, in Taiwanese and Singaporean children (NCT00892775).

Methods:Healthy children aged 11–22 mo were randomized to receive two doses of either the MMRV _{new WS} vaccine or the MMRV vaccine. Antibody titers against measles, mumps and rubella were measured using ELISA and against varicella using an immunofluorescence assay. The primary objective was to demonstrate non-inferiority of MMRV_{new WS} to MMRV in terms of post-dose-1 seroconversion rates, defined as a group difference with a lower limit of the 95% confidence interval greater than -10% for each antigen. Parents/guardians recorded symptoms in diary cards for 43 d after each vaccine dose.

Results:Non-inferiority of MMRV _{new WS} to MMRV was achieved for all vaccine antigens. The lower limits of the 95% confidence intervals for group differences (MMRV_{new WS} group vs. MMRV) for measles (99.4% vs 100%), mumps (89.7% vs 90.4%), rubella (99.7% vs 100%) and varicella (97.6% vs 92.9%) seroconversion rates were greater than -10%. Mild symptoms including a peak in fever between days 5 and 12, post-dose-1, was observed in both groups.

Conclusion:The immune responses elicited by the MMRV _{new WS} vaccine were non-inferior to that elicited by the MMRV vaccine for all antigens. Both vaccines exhibited an acceptable safety profile in Taiwanese and Singaporean children.

Keywords: :

• immunogenicity
• MMRV vaccine
• newly established working seed virus stock
• safety
• Singapore
• Taiwan

Disclosure of Potential Conflicts of Interest

L.M.H. and L.B.W. declare to have received payment for consultancy for being on the advisory board and their institutions received grants to conduct clinical trials, authors (L.M.H., L.B.W. and C.P.C.) declare either they/institution received payment for lectures including service on speakers bureaus and support for travel to meetings for the study or other purposes. M.P. and O.H. are employed by the GlaxoSmithKline group of companies.

This study was sponsored and funded by GlaxoSmithKline Biologicals S.A., Rixensart, Belgium. GlaxoSmithKline Biologicals S.A. was involved in all stages of the study conduct and analysis; and also took charge of all costs associated with the development and the publishing of the manuscript.

Acknowledgments

The authors thank all the investigators involved in this clinical trial conducted in Taiwan and Singapore. The authors also thank the study nurses and other staff members involved and the parents and children who participated in the study. The authors acknowledge Christopher da Costa (ex-employee of GSK Vaccines) for his contributions on the study design; Bruce Innis for his critical contributions to the overall study design and interpretation of the data; Pierre Cambron for serology testing; Ann Delforge for study coordination; Valerie Balosso for clinical data coordination; Ashmita Ravishankar for manuscript writing and K Manjula for publication management (all employees of GSK Vaccines).

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