ObjectivesThis study aimed to identify the specific vaccine strain associated with herpes zoster in children following a series of diagnosed cases and to explore whether differences in single nucleotide polymorphisms (SNPs) among various vaccine strains are linked to an increased incidence of herpes zoster after vaccination. MethodsFrom February 2021 to March 2024, children <12 years old suspected of vaccine-related varicella-like rash or HZ were included. Varicella zoster virus DNA isolated from the patients were sequenced to differentiate vaccine type versus wild type. 3D protein structures of pORF62 were simulated using ORF62 sequences extracted from whole genome sequencing of vOka, MAV/06, Oka/SK vaccines, and pOka reference. ResultsA total of 27 children with a median age of 2.1 (IQR, 1.5–3.4) years old presented with vaccine-related varicella-like rash (n=4/27, 14.8%) or HZ (n=23/27, 85.2%). One patient with varicella-like rash and 34.8% (n=8/23) with HZ had disseminated skin involvement. All were immunized with the Oka/SK strain varicella vaccine. Genotyping showed 88.2% (n=15/17) had SNPs specific to the Oka/SK strain and two had SNPs considered pOka type contained within the Oka/SK vaccine. Despite accumulations of SNPs in ORF 62 of Oka/SK, the translated amino acid sequence and 3D protein structure were identical to wild-type pOka’s pORF62. In vOKA and MAV/06, changes in amino acids occurred at two positions, S628G and R958G, within pORF62. The predicted 3D protein structure of vOka and MAV/06’s pORF62 showed that the alpha helical structure within region I undergoes conformational change potentially increasing difficulties in interactions with infection-related proteins thereby decreasing virulence. pORF62 in pOka and Oka/SK exhibited more stable structure complex of the alpha helical structure. ConclusionsLack of structural alternations in region I of pORF62 due to the absence of critical genetic polymorphisms in ORF62 could be associated with the heightened incidence of adverse events.