Population diversity in batches of the varicella Oka vaccine

Abstract

The Oka vaccine is a live attenuated vaccine for the prevention of varicella. Although the vaccine differs from the progenitor virus by over 40 mutations, only three of these are fixed, the rest being a mixture of the wild-type and the vaccine allele. To examine the extent of this variability between two of the three commercially available vaccine preparations, we analysed the vaccine/wild-type allele frequencies present at fifteen vaccine loci in five preparations each from two different manufacturers of the vOka vaccine. Our results suggest that differences in manufacturing processes between the two companies have resulted in significant variation in the frequencies of the vaccine/wild-type alleles in their vaccines. Yet despite these differences, the allele frequencies in the vaccines from the two companies are strongly correlated. We discuss the significance of these findings and the role of evolutionary processes that influence the production of this live attenuated vaccine.

Clinical and molecular aspects of the live attenuated Oka varicella vaccine

“…*, Where passage levels are given next to an "a", these have been inferred from a and b. The World Health Organization guidelines indicate a limit for Oka strain varicella vaccine at passage level 38; hence, final passage numbers in MRC5 cells can be estimated [101] skin homing markers CLA and CCR4 [112]. Like wild type, vOka infects CD4 + , CD8 + , and CD4 + CD8 + T-lymphocyte populations in the SCID-hu mouse model carrying human fetal thymus/liver implants [113].…”

“…However, recent analysis of these three loci in Varivax-derived ORF 62 TA clones detected the wild-type allele on 2% of clones at position 107252 and on 6% of clones at 106262 and 108111 [100,169]. The wild type at these positions was probably not detected in previous studies either due to the sensitivity limits of Sanger sequencing, which was the method used to sequence the three commercial vaccine preparations [95,98] or because of the genetic variation between different vaccine lots [97,100,101]. Position 107252 seems to be a particularly unreliable marker.…”

“…Over 90% of these were present on less than 10% of genomes and would therefore have been missed by traditional Sanger methods used for previous whole‐genome sequencing of vOka preparations . In addition to differences in the sequence of the three commercial vaccine preparations, variation has also been reported in the genetic composition of Varilrix when compared with Varivax (Table ). There is evidence to suggest that such differences affect immunogenicity of the vaccines.…”

“…*, Where passage levels are given next to an “a”, these have been inferred from a and b. The World Health Organization guidelines indicate a limit for Oka strain varicella vaccine at passage level 38; hence, final passage numbers in MRC5 cells can be estimated …”

“…However, the emergence of Oka‐like strains in the USA and Australia has led to the need for alternative and more reliable markers . Three loci in ORF 62 at positions 106262, 107252, and 108111 have been reported as fixed for the vOka allele in all commercial vaccine preparations and present in all vOka haplotypes from varicella and zoster rashes . As all three of these sites in ORF 62 were deemed equally robust at discriminating between vOka and wild type, some laboratories often only characterize one, either alone or in combination with the Bgl I and Pst I sites .…”