title: Clinical and molecular aspects of the live attenuated Oka varicella vaccine.
abstract: VZV is a ubiquitous member of the Herpesviridae family that causes varicella (chicken pox) and herpes zoster (shingles). Both manifestations can cause great morbidity and mortality and are therefore of significant economic burden. The introduction of varicella vaccination as part of childhood immunization programs has resulted in a remarkable decline in varicella incidence, and associated hospitalizations and deaths, particularly in the USA. The vaccine preparation, vOka, is a live attenuated virus produced by serial passage of a wild-type clinical isolate termed pOka in human and guinea pig cell lines. Although vOka is clinically attenuated, it can cause mild varicella, establish latency, and reactivate to cause herpes zoster. Sequence analysis has shown that vOka differs from pOka by at least 42 loci; however, not all genomes possess the novel vOka change at all positions, creating a heterogeneous population of genetically distinct haplotypes. This, together with the extreme cell-associated nature of VZV replication in cell culture and the lack of an animal model, in which the complete VZV life cycle can be replicated, has limited studies into the molecular basis for vOka attenuation. Comparative studies of vOka with pOka replication in T cells, dorsal root ganglia, and skin indicate that attenuation likely involves multiple mutations within ORF 62 and several other genes. This article presents an overview of the clinical aspects of the vaccine and current progress on understanding the molecular mechanisms that account for the clinical phenotype of reduced virulence.
authors.affiliation: Division of Infection and Immunity, University College London, London, UK.
authors.forename: Mark
authors.initials: M
authors.lastname: Quinlivan
authors.forename: Judy
authors.initials: J
authors.lastname: Breuer
mesh_terms: D000818:Animals; D002460:Cell Line; D002644:Chickenpox / Q000821:virology; D019433:Chickenpox Vaccine / Q000009:adverse effects* / Q000235:genetics* / Q000276:immunology; D004279:DNA, Viral / Q000737:chemistry / Q000235:genetics; D006168:Guinea Pigs; D006562:Herpes Zoster / Q000821:virology; D006801:Humans; D017354:Point Mutation; D017422:Sequence Analysis, DNA; D012692:Serial Passage; D014613:Vaccines, Attenuated / Q000009:adverse effects / Q000235:genetics / Q000276:immunology; D014775:Virus Activation; D014776:Virus Cultivation; D017735:Virus Latency
chemical_list: D019433:Chickenpox Vaccine; D004279:DNA, Viral; D014613:Vaccines, Attenuated