Immunogenicity and safety of an investigational varicella zoster vaccine in toddlers aged 12–15 months: results of a phase II, controlled, randomized trial

Varicella is an acute, highly contagious infectious disease that primarily impacts young children with approximately 90% of cases occurring under the age of 15. Due to the high incidence of varicella infection, the potential for serious complications, and the significant economic and public health burden, vaccination of toddlers against varicella is included in routine vaccination programs in many countries. This study assessed the immunogenicity and safety of the investigational varicella vaccine (VNS) compared to a licensed, current standard-of-care vaccine. In this phase II, observer-blind, randomized, multicenter, controlled study, toddlers (12 to 15 months of age) received a single dose of the VNS vaccine (low, medium or high potency), or a single dose of the control vaccine. Hepatitis A and measles-mumps-rubella vaccines were co-administered to all participants. Pneumococcal conjugate vaccine was co-administered to all study participants as per national recommendations. Immunogenicity was assessed 43 days after vaccination; safety data were collected for up to 181 days post-vaccination. Overall, 800 participants were enrolled from 55 study centers across four countries (Estonia, Poland, Taiwan, and the United States), of whom 765 (95.6%) completed the study. Anti-varicella zoster virus glycoprotein E antibody geometric mean concentrations were generally comparable across study groups (960 mIU/ml 95% confidence interval [CI: 843–1093], 1071 mIU/ml 952–1204 and 1555 mIU/ml 1407–1718 in the VNS-Low, VNS-Med and VNS-High groups, versus 1284 mIU/ml 1136–1453 in the control group). Seroresponse rates at Day 43 ranged from 93.6% in the VNS-Low group to 98.7% in the VNS-High group and 98.1% in the control group. The rate of occurrence, severity, and duration of adverse events and serious adverse events were similar across all study groups. These results show that the VNS vaccine was immunogenic with an acceptable safety profile following a single dose of all three potencies. Clinical trial registration number: NCT05084508 • Varicella is an acute, highly contagious infectious disease primarily affecting young children. • Three potencies of an investigational varicella vaccine were administered as a single dose. • The investigational varicella vaccine was compared to a standard of care vaccine. • All three potencies of the investigational vaccine formulation were immunogenic. • The safety profile of all three potencies of the investigational vaccine was acceptable.