Varicella (chickenpox) is a widespread, highly contagious disease caused by varicella-zoster virus (VZV). Serious complications of varicella include secondary bacterial infection, pneumonia, encephalitis, congenital infection, and, rarely, death (4, 21). Following the acute infection, VZV establishes a lifelong latent infection in neurosensory ganglia that commonly reactivates to cause zoster, typically in elderly or immunocompromised patients (24). A safe and effective live-attenuated varicella vaccine was developed in 1968 and has been licensed and recommended in the United States since 1995 (25). Commercial varicella vaccines (all of which are derived from the Japanese Oka strain) have never been cloned, and complete genomic sequencing of the V-Oka-Biken vaccine revealed that it contained several strains that could be separated in tissue culture (9, 10). Three manufacturers (Merck & Co Inc., Pasteur Merieux Connaught, and Biken Inc.) accepted the original V-Oka vaccine preparations, and each has the vaccine in production, with some variation in manufacturing processes. GlaxoSmithKline (Uxbridge, United Kingdom) reported the use of a selected, plaque-purified variant of V-Oka vaccine (2, 7). V-Oka has been used successfully for vaccination in the United States, Canada, Australia, Japan, and South Korea. In some European countries, varicella vaccination is recommended for persons at risk of severe chickenpox and/or for seronegative health care workers. Germany also recommends varicella vaccination for adolescents with no history of chickenpox (23). The vaccine provides 90% protection from any disease and over 95% protection from moderate to severe disease (8).V-Oka is known to establish latent infection in the dorsal root ganglia, and zoster has been demonstrated as a rare adverse consequence among vaccinees (8,13,14,22,26). However, in all of these cases, the status of vaccine-specific mutations was not documented. In addition, the primary DNA sequence was not compared to that of the material used for vaccination. Until recently, laboratories evaluated only three single nucleotide polymorphism (SNP) mutations in open reading frames (ORFs) 38, 54, and 62 to differentiate V-Oka from wild-type strains, but only the ORF 62 SNP reliably differentiates Japanese genotype wild-type strains from vaccine (15,20). Conceivably, genomic mutations or reversions to wild type, particularly those that confer amino acid substitutions, could affect virulence and restore wild-type pathogenicity. Furthermore, VZV strains with unique pathogenic qualities could emerge. The comparison of DNA sequences between V-Oka and P-Oka revealed 42 base substitutions associated with 20 amino acid changes (11). Specific amino acid substitutions in ORF 62 have been associated with enhanced virus growth and spread in cell culture, and substrains purified from the vaccine mixture display variable properties in cell culture (11).This study sought to compare vaccine mutations associated with amino acid changes in V-Oka-GSK to published V-OkaBiken and ...