title: Deep Sequencing of Distinct Preparations of the Live Attenuated Varicella-Zoster Virus Vaccine Reveals a Conserved Core of Attenuating Single-Nucleotide Polymorphisms.
abstract: The continued success of the live attenuated varicella-zoster virus vaccine in preventing varicella-zoster and herpes zoster is well documented, as are many of the mutations that contribute to the attenuation of the vOka virus for replication in skin. At least three different preparations of vOka are marketed. Here, we show using deep sequencing of seven batches of vOka vaccine (including ZostaVax, VariVax, VarilRix, and the Oka/Biken working seed) from three different manufacturers (VariVax, GSK, and Biken) that 137 single-nucleotide polymorphism (SNP) mutations are present in all vaccine batches. This includes six sites at which the vaccine allele is fixed or near fixation, which we speculate are likely to be important for attenuation. We also show that despite differences in the vaccine populations between preparations, batch-to-batch variation is minimal, as is the number and frequency of mutations unique to individual batches. This suggests that the vaccine manufacturing processes are not introducing new mutations and that, notwithstanding the mixture of variants present, VZV live vaccines are extremely stable.
  
  
  
  The continued success of vaccinations to prevent chickenpox and shingles, combined with the extremely low incidence of adverse reactions, indicates the quality of these vaccines. The vaccine itself is comprised of a heterogeneous live attenuated virus population and thus requires deep-sequencing technologies to explore the differences and similarities in the virus populations between different preparations and batches of the vaccines. Our data demonstrate minimal variation between batches, an important safety feature, and provide new insights into the extent of the mutations present in this attenuated virus.
authors.affiliation: MRC Centre for Medical Molecular Virology, Division of Infection and Immunity, London, United Kingdom d.depledge@ucl.ac.uk.
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Depledge
authors.affiliation: The Research Foundation for Microbial Diseases of Osaka University, Biken, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Yamanishi
authors.affiliation: The Research Foundation for Microbial Diseases of Osaka University, Biken, Japan.
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Gomi
authors.affiliation: Division of Infectious Disease, Columbia University Medical Center, New York, New York, USA.
authors.forename: Anne A
authors.initials: AA
authors.lastname: Gershon
authors.affiliation: MRC Centre for Medical Molecular Virology, Division of Infection and Immunity, London, United Kingdom.
authors.forename: Judith
authors.initials: J
authors.lastname: Breuer
mesh_terms: D019433:Chickenpox Vaccine / Q000235:genetics*; D014645:Herpesvirus 3, Human / Q000235:genetics* / Q000472:pathogenicity; D059014:High-Throughput Nucleotide Sequencing; D020641:Polymorphism, Single Nucleotide; D014613:Vaccines, Attenuated / Q000235:genetics; D014774:Virulence
chemical_list: D019433:Chickenpox Vaccine; D014613:Vaccines, Attenuated