Identification of Five Major and Two Minor Genotypes of Varicella-Zoster Virus Strains: a Practical Two-Amplicon Approach Used To Genotype Clinical Isolates in Australia and New Zealand
Whole genome phylogenetic analysis in this study resolved a total of five major genotypes among the 22 varicella-zoster virus (VZV) strains or isolates for which complete genomic sequences are available.
Acquiring one strain can result in immunity to all strains of the virus. In some cases, however, complete immunity is not attained and an individual can become re-infected.
Shingles, or herpes zoster, this is a later reactivation of latent virus. It can occur any time after the initial infection. Usually, it occurs years later, and is activated by stress or an unbalanced immune system.
Varicella Zoster Virus
VZV is a member of the herpes virus group or (alpha) herpes virus 3, and it is a DNA virus. VZV can persist as a latent infection in dorsal root or extra medullary cranial ganglia.
…wild-type varicella-zoster virus (VZV) strains to seven genotypes: A1, A2, J1, B1, B2, C, and C1. VZV isolates identified as E (ORF22 method) had the genetic signature of genotype C VZV strains, M1 strains were A1, and M2 were A2. No J strains were detected, but parental Oka and vaccine Oka (genotype J) corresponded to genotype J1. M4 isolates (B) share the SNP array observed for M1 and E viruses, and probably represent recombinants between African-Asian (M1) and European (E) viruses. The two genotyping methods, using entirely different genomic targets, produced identical clusters for the strains examined, suggesting robust phylogenetic linkages among VZV strains circulating in Europe.
pOka is the parental Oka strain from which varicella vaccine was derived. Sequence positions are based on the published genomic sequence for the Dumas strain. Green cells indicate European genotype (E) markers; yellow cells are Japanese genotype (J) markers, rose cells are markers unique to various M genotype variants, and uncolored cells reflect markers that are consistent across genotypes. ND, not determined.
VZV is a member of the herpesvirus family. It has 71 genes, all of which are expressed in lytic infection and seven of which are expressed in latent infection (5). Only neurons support latent infection. There is one serotype, but several genotypes are known, with small differences in their DNAs, classified as European, Japanese, and Mosaic (6). Recently, 3% of VZV strains circulating in the United States of America have been identified as Japanese type (7).
VZV was successfully attenuated by Takahashi and colleagues in 1974, by serial passage of a clinical isolate from an otherwise healthy boy with chickenpox (13).
Attenuation was achieved by passage 11 times at 34ºC in human embryonic lung fibroblasts (HELF), 12 passages at 37ºC in guinea-pig fibroblasts, and 5 to 6 passages in MRC -5 human fibroblasts at 37ºC. Infected cell suspensions were sonicated to obtain cell-free VZV.Standard safety-testing after injection into small mammals was also performed, and did not identify any adventitious agents.
Varicella vaccines contain a mixture of Oka and parental strains (14-16). Sequencing of the Dumas strain of wild-type VZV, and the Oka strain, has shown that there are 42 differing bases, over one third of which are in gene 62.Three fixed mutations have been identified in Oka strains present in skin rashes of vaccinees, all located in gene 62 (15,17,18). Although the genetic basis for attenuation is still unknown, it is possible to differentiate Oka from wild-type VZV by PCR in clinical specimens (8).
Monovalent varicella vaccine is produced in the United States (VarivaxTM; Merck & Co., Inc.), the Kingdom of Belgium (VarilrixTM; GlaxoSmithKline), and Japan (OKAVAX™; Biken, distributed by Aventis Pasteur). These vaccines vary slightly in passage number in human diploid cells, antibiotics for sterility, stabilizers and minor constituents. Each preparation guarantees 1350 plaque forming units (PFU) per 0.5 ml at expiration; doses at release vary from 3 000 to 17 000 PFU.
Combination vaccines for measles-mumps-rubella-varicella (MMRV) are produced by Merck (ProQuadTM)and GSK (Priorix-TetraTM). MMRV vaccines are licensed for children 12 months to 12 years old. They contain the same measlesmumps-rubella (MMR) components as MMR vaccine, but have a higher concentration of Oka varicella vaccine (~ 10 000 PFU at expiration) than monovalent varicella vaccines.
A formulation of the Oka strain containing~ 17 000 PFU (ZostavaxTM), is used for prevention of zoster when administered to healthy adults above the age of 60 years.
VARIVAX* [Varicella Virus Vaccine Live] is a preparation of the Oka/Merck strain of live, attenuated varicella virus. The virus was initially obtained from a child with natural varicella, then introduced into human embryonic lung cell cultures, adapted to and propagated in embryonic guinea pig cell cultures and finally propagated in human diploid cell cultures (WI-38). Further passage of the virus for varicella vaccine was performed at Merck Research Laboratories (MRL) in human diploid cell cultures (MRC-5) that were free of adventitious agents. This live, attenuated varicella vaccine is a lyophilized preparation containing sucrose, phosphate, glutamate, and processed gelatin as stabilizers.
ZOSTAVAX is a lyophilized preparation of live, attenuated varicella-zoster virus (Oka/Merck) to be reconstituted with sterile diluent to give a single dose suspension with a minimum of 19,400 PFU (plaque forming units) when stored at room temperature for up to 30 minutes.
(no longer available until further notice)
ProQuad* is a combined attenuated live virus vaccine containing measles, mumps, rubella, and varicella viruses. ProQuad is a sterile lyophilized preparation of (1) the components of M-M-R*II (Measles, Mumps and Rubella Virus Vaccine Live): Measles Virus Vaccine Live, a more attenuated line of measles virus, derived from Enders’ attenuated Edmonston strain and propagated in chick embryo cell culture; Mumps Virus Vaccine Live, the Jeryl Lynn™ (B level) strain of mumps virus propagated in chick embryo cell culture; Rubella Virus Vaccine Live, the Wistar RA 27/3 strain of live attenuated rubella virus propagated in WI-38 human diploid lung fibroblasts; and (2) Varicella Virus Vaccine Live (Oka/Merck), the Oka/Merck strain of varicella-zoster virus propagated in MRC-5 cells. The cells, virus pools, bovine serum, and human albumin used in manufacturing are all tested to provide assurance that the final product is free of potential adventitious agents.
ProQuad, when reconstituted as directed, is a sterile preparation for subcutaneous administration. Each 0.5-mL dose contains not less than 3.00 log10 TCID50 (50% tissue culture infectious dose) of measles virus; 4.30 log10 TCID50 of mumps virus; 3.00 log10 TCID50 of rubella virus; and a minimum of 3.99 log10 PFU (plaque-forming units) of Oka/Merck varicella virus.