Molecular studies of the Oka varicella vaccine

Varicella zoster virus (VZV) is one of eight members of the Herpesviridae family for which humans are the primary host; it causes two distinct diseases, varicella (chickenpox) and zoster (shingles). Varicella results from primary infection, during which the virus establishes latency in sensory neurons, a characteristic of all members of the Alphaherpesvirinae subfamily. Zoster is caused by reactivation of latent virus, which typically occurs when cellular immunity is impaired. VZV is the first human herpesvirus for which a vaccine has been licensed. The vaccine preparation, v-Oka, is a live-attenuated virus stock produced by the classic method of tissue culture passage in animal and human cell lines. Over 90 million doses of the vaccine have been administered in countries worldwide, including the USA, where varicella morbidity and mortality has declined dramatically. Over the last decade, several laboratories have been committed to investigating the mechanism by which the Oka vaccine is attenuated. Mutations have accumulated across the genome of the vaccine during the attenuation process; however, studies of the contribution of these changes to vaccine attenuation have been hampered by the lack of a suitable animal model of VZV disease and by the heterogeneity that exists among the viral population within the vaccine preparation. Notwithstanding, a wealth of data has been generated using various laboratory methodologies. Studies of the vaccine virus in human xenografts implanted in severe combined immunodeficiency-hu mice, have enabled analyses of the replication dynamics of the vaccine in dorsal root ganglia, T lymphocytes and skin. In vitro assays have been used to investigate the effect of vaccine mutations on viral gene expression and sequence analysis of vaccine rash viruses has permitted investigations into spread of the vaccine virus in a human host. We present here a review of what has been learned thus far about the molecular and phenotypic characteristics of the Oka vaccine.