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Varicella-zoster virus (VZV) infections cause a substantial disease burden, which is underestimated due to incomplete reporting data and lack of serological surveillance. In this post-hoc analysis of a randomized, Phase IIIb clinical trial (NCT00226499) with a ten-year follow-up period, we report anti-VZV antibody levels and persistence in non-vaccinated children, as a varicella infection estimate in ten European countries with endemic varicella. The present analysis specifically focuses on clinical and serological data from the control group, which included 827 healthy participants aged 12–22 months who received two doses of measles-mumps-rubella (MMR) vaccine. The per-protocol cohort included 744 children for whom varicella occurrence was evaluated by clinical definitions, epidemiological links and PCR test outcomes. Anti-VZV antibody levels were assessed by ELISA. The primary objective of this analysis was to correlate varicella occurrence with anti-VZV antibody levels. Varicella was confirmed in 47% of MMR recipients. Among participants without reported varicella, the percentage of anti-VZV seropositive children increased to 75% and average anti-VZV antibody concentrations increased to 250 mIU/mL at year ten after vaccination, suggesting infection or exposure. An eight-fold increase in anti-VZV antibody concentrations between two consecutive visits, which is also observed after confirmed varicella, was detected in 37% of these participants during the follow-up period. About one-third of children not vaccinated against varicella and not diagnosed with varicella developed an anti-VZV immune response, suggesting subclinical varicella occurrence. Longitudinal studies combining serology and disease incidence are necessary to reliably estimate total varicella burden of infection.

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 (MMRVnew 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 MMRVnew 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 (MMRVnew 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.