ArticleProceedings of the National Academy of Sciences of the United States of America2007
Natural selection for rash-forming genotypes of the varicella-zoster vaccine virus detected within immunized human hosts.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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21 citing papers in PubMed, 53 citations in OpenAlex.
- The live attenuated varicella-zoster virus vaccine vOka: Molecular and cellular biology of its skin attenuation.Human vaccines & immunotherapeutics · 2025Review
- Perspectives on the History and Epidemiology of the Varicella Virus Vaccine and Future Challenges.Pathogens (Basel, Switzerland) · 2025Review
- Upregulation of keratin 15 is required for varicella-zoster virus replication in keratinocytes and is attenuated in the live attenuated vOka vaccine strain.Virology journal · 2024Article
- Creating the "Dew Drop on a Rose Petal": the Molecular Pathogenesis of Varicella-Zoster Virus Skin Lesions.Microbiology and molecular biology reviews : MMBR · 2023Review
- Insights From Studies of the Genetics, Pathogenesis, and Immunogenicity of the Varicella Vaccine.The Journal of infectious diseases · 2022Article
- Application of Next-Generation Sequencing to Reveal How Evolutionary Dynamics of Viral Population Shape Dengue Epidemiology.Frontiers in microbiology · 2020Review
- Varicella and herpes zoster vaccine development: lessons learned.Expert review of vaccines · 2017Review
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- Deep sequencing of viral genomes provides insight into the evolution and pathogenesis of varicella zoster virus and its vaccine in humans.Molecular biology and evolution · 2014Article
- Novel genetic variation identified at fixed loci in ORF62 of the Oka varicella vaccine and in a case of vaccine-associated herpes zoster.Journal of clinical microbiology · 2012Article
- Molecular analysis of varicella vaccines and varicella-zoster virus from vaccine-related skin lesions.Clinical and vaccine immunology : CVI · 2011Article
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- Article
- Varicella-zoster virus immediate-early protein 62 blocks interferon regulatory factor 3 (IRF3) phosphorylation at key serine residues: a novel mechanism of IRF3 inhibition among herpesviruses.Journal of virology · 2010Article
- A varicella-zoster virus mutant impaired for latency in rodents, but not impaired for replication in cell culture.Virology · 2010Article
- Transmission of varicella vaccine virus, Japan.Emerging infectious diseases · 2009Article
- Identification of mutations in a temperature-sensitive mutant (tsm5) of murine cytomegalovirus using complementary genome sequencing.Journal of medical virology · 2009Article
- Complete DNA sequences of two oka strain varicella-zoster virus genomes.Journal of virology · 2008Article
- Severe complications of chickenpox in hospitalised children in the UK and Ireland.Archives of disease in childhood · 2007Article
- Dengue virus evolution and virulence models.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2007Article
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7 authors at 2 institutions in 2 countries.
Funding
Abstract
The Oka vaccine strain is a live attenuated virus that is routinely administered to children in the United States and Europe to prevent chickenpox. It is effective and safe but occasionally produces a rash. The vaccine virus has accumulated mutations during its attenuation, but the rashes are not explained by their reversion, unlike complications reported for other viral vaccines. Indeed, most of the novel mutations distinguishing the Oka vaccine from the more virulent parental virus have not actually become fixed. Because the parental alleles are still present, the vaccine is polymorphic at >30 loci and therefore contains a mixture of related viruses. The inoculation of >40 million patients has consequently created a highly replicated evolutionary experiment that we have used to assess the competitive ability of these different viral genotypes in a human host. Using virus recovered from rash vesicles, we show that two vaccine mutations, causing amino acid substitutions in the major transactivating protein IE62, are outcompeted by the ancestral alleles. Standard interpretations of varicella disease severity concentrate on the undeniably important effects of host genotype and immune status, yet our results allow us to demonstrate that the viral genotype is associated with virulence and to identify the key sites. We propose that these loci have pleiotropic effects on the immunogenic properties of the virus, rash formation, and its epidemiological spread, which mould the evolution of its virulence. These findings are of practical importance for reducing the incidence of vaccine-associated rash and promoting public acceptance of the vaccine.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.