Abstract
Varicella-zoster virus (VZV) infection results in varicella mostly in children. Reactivation of the virus causes herpes zoster (HZ), mostly in adults. A live attenuated vaccine (vOka-Biken) was originally derived from the parental strain pOka. Several live attenuated vaccines based on the Oka strain are currently available worldwide. In China, varicella vaccines have been licensed by four manufacturers. In this study, we analyze the whole-genome sequence (WGS) of vOka-BK produced by Changchun BCHT Biotechnology also known as Baike. vOka-BK WGS was compared against the genomic sequences of four other Oka strains: pOka, vOka-Biken, vOka-Varilrix from GlaxoSmithKline, and vOka-Varivax from Merck & Co. A previous study identified 137 single nucleotide polymorphisms (SNPs) shared by all vOkas. The current analysis used these data as a reference to compare with vOka-BK WGS and focused on 54 SNPs located in the unique regions of the genome. Twenty-eight nonsynonymous substitutions were identified, ORF62 and ORF55 featuring the most amino acid changes with 9 and 3, respectively. Among the 54 SNPs, 10 had a different mutation profile in vOka-BK compared to the other three vaccines. A comparison with the clade 3 strain Ellen, known to be attenuated, identified three shared amino acid changes: *130R in ORF0 and R958G and S628G in ORF62. This analysis provides the first comparison of a Chinese varicella vaccine to the other vaccines available worldwide and identifies sites potentially critical for VZV vaccine efficacy.IMPORTANCE Varicella, also known as chickenpox, is a highly contagious disease, caused by varicella-zoster virus (VZV). Varicella is a common childhood disease that can be prevented by a live attenuated vaccine. The first available vaccine was derived from the parental Oka strain in Japan in 1974. Several live attenuated vaccines based on the Oka strain are currently available worldwide. Among the four vaccines produced in China, the vaccine manufactured by Changchun BCHT Biotechnology, also known as Baike, has been reported to be very efficacious. Comparative genomic analysis of the Baike vaccine with other Oka vaccine strains identified sites that might be involved in vaccine efficacy, as well as important for the biology of the virus.
Highlights
IMPORTANCE Varicella, known as chickenpox, is a highly contagious disease, caused by varicella-zoster virus (VZV)
Additional studies on the clade 3 strain Ellen, which became highly attenuated after at least 90 passages in cultured cells, showed that position 560 within ORF0 and positions 106262 and 107252 with ORF62 were likely to be associated with attenuation [14]
Kaufer et al demonstrated that ORF0 is essential for Varicella-zoster virus (VZV) replication and could be considered a functional homolog of HSV-1 UL56 [18]
Summary
IMPORTANCE Varicella, known as chickenpox, is a highly contagious disease, caused by varicella-zoster virus (VZV). Several live attenuated vaccines based on the Oka strain are currently available worldwide. VZV is the causative agent of varicella (chickenpox) mostly in children It establishes latency in the sensory ganglia with the potential to reactivate at a later time to cause herpes zoster (HZ), known as shingles. Most live attenuated varicella vaccines were derived from the same parental strain (pOka) of wild-type VZV [3, 4]. GlaxoSmithKline (GSK) Biologicals and Merck Sharp & Dohme (Merck & Co.) have produced their own formulations of the Oka vaccine, known as Varilrix and Varivax, respectively, which were both derived from the Biken seed stock. Varilrix was first licensed in some European countries in 1984, whereas Varivax was approved in the United States in 1995 [4]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
