VIS—Varicella (Chickenpox) Vaccine
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Varicella-zoster virus (VZV) is the etiological agent of both varicella (chickenpox) and herpes zoster (shingles). Primary infection with VZV causes varicella, which usually occurs in childhood. Reactivation of VZV in previously infected individuals results in a herpes zoster that occurs most commonly in the elderly. In 1974, a live-attenuated VZV strain was established and subsequently licensed for vaccination in Japan (1). Comparison of the complete DNA sequences of the Oka vaccine strain (vOka) and the parental Oka strain (pOka) revealed there were only 42 nucleotide substitutions along the whole 125-kbp viral genome, 15 of which were located in the major transactivator ORF62 region (2). The high sequence homology between vOka and pOka increases the difficulty of distinguishing vOka from clinical isolates with the pOka genotype. The pOka-like wild-type strain constitutes 20–30% of all VZV isolates in Japan (3). In contrast, it seems a rare genotype in other countries such as the U.S. and Australia (4,5). In this study we report a case of herpes zoster infected by the pOka-like wild-type strain in a Chinese woman. A 27-year-old woman who was 8 months pregnant presented to the First Affiliated Hospital of Anhui Medical University (Hefei, China) with vesicle skin lesions. The diagnosis of zoster was made mainly based on the history and features of the rash. The zoster rashes had developed on the right side of her abdomen, and she had no post-herpetic neuralgia. VZV was isolated in human embryonic lung fibroblasts from vesicle fluid taken from the patient on day 2 after the onset of zoster and was identified by immunocytochemistry with monoclonal antibodies to VZV glycoprotein E (Biodesign International ® , Saco, Maine, USA). This strain is hereafter designated as ZW strain. Serologic assay by fluorescent antibody to the membrane antigen (FAMA) test revealed a specific VZV IgG antibody titer of 1:8 in the serum colleted on day 2, and 1:256 in the second serum specimen obtained 16 days after the onset of symptoms. Viral DNA was extracted from the fluid of the rash vesicles
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Varicella zoster virus
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Approximately 15% of recipients of live attenuated varicella vaccine may develop mild breakthrough varicella months to years after immunization. Although some vaccinees will develop zoster, it is less common in recipients of vaccine than in those who have had natural varicella.To determine the varicella-zoster virus (VZV) strain responsible for breakthrough varicella and zoster in recipients of varicella vaccine.A PCR assay capable of distinguishing wild-type from vaccine strain VZV was performed on samples from skin lesions from vaccinees with breakthrough varicella and zoster.All of 57 vaccinees with breakthrough varicella, clinically diagnosed on the basis of a generalized maculopapular or vesicular rash, in which there was amplifiable DNA [corrected], had wild-type VZV infection based on analysis of viral DNA. The Oka vaccine strain of VZV was not identified in any of these cases. In contrast, in 32 patients with zosteriform rashes, the vaccine strain was identified in 22 samples, and the wild-type strain was identified in 10 samples.Wild-type virus was identified in all generalized rashes occurring after the immediate 6-week postvaccination period. When reactivation of vaccine strain occurred, it presented as typical zoster. We find no evidence that reactivation of vaccine virus occurs with the clinical picture of generalized rash.
Varicella zoster virus
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Maculopapular rash
Chicken Pox
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Varicella zoster virus
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In Japan and the United States, where vaccination against varicella-zoster virus (VZV) infection with the live attenuated Oka strain of varicella is routine, cases of chickenpox or shingles occurring in vaccinees can be caused by either wild-type or vaccine virus. Differentiating such cases is important epidemiologically and can be achieved only using molecular typing methods. In the United Kingdom, the Oka vaccine is being considered for use in groups at risk of severe primary varicella, such as seronegative immunocompromised patients and women who may be considering pregnancy. In addition, seronegative health workers who may be occupationally exposed to VZV infection might also be offered vaccination. We analysed 249 U.K. wild-type VZV strains, 105 from cases of chickenpox and 144 from shingles cases, to determine whether they could be distinguished from Oka by the genotyping systems used in Japan and the United States. Four polymorphic loci were examined, a Pst 1 restriction site in gene 38, a Bgl 1 restriction site in gene 54, the R5 repeat region, and the R2 repeat region. The results suggest that U.K. strains of VZV are more similar to U.S. strains than to Japanese strains. All the U.K. wild-type viruses were positive for the Pst 1-1 restriction site, unlike Oka, which is negative. However, one of thirty strains was indistinguishable from Oka at all other loci. J. Med. Virol. 53:60–62, 1997. © 1997 Wiley-Liss, Inc.
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A polymerase chain reaction (PCR) assay that identifies and differentiates wild-type (wt) and vaccine strains of varicella-zoster virus (VZV) was used to determine if VZV strains with restriction fragment length polymorphisms resembling those of the Japanese Oka vaccine strain were present in the wt pool outside of Japan. Virus samples (n = 114) from patients with chickenpox and zoster from various parts of the United States and Australia were analyzed. The assay correctly identified 113 samples as wt strain. The 1 sample identified as Oka vaccine strain came from a child with leukemia who developed a vaccine-associated rash after receiving the live attenuated varicella vaccine. At this point, there is no evidence that wt strains resembling the vaccine are circulating outside of Japan. This indicates that this PCR assay can be utilized to distinguish rashes due to vaccine and wt VZV.
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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.
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Little is known about the pathogenic potential of individual strains in the varicella vaccine. We analyzed genomic variation among specimens obtained from vaccine recipients with postvaccination rash or herpes zoster (HZ), focusing on polymorphisms between live attenuated varicella vaccine virus and wild-type varicella-zoster virus. Eleven of 18 postvaccination HZ specimens contained >1 strain, and 7 of 18 appeared to be clonal. All 21 postvaccination rash specimens contained mixtures of vaccine strains. Four single-nucleotide polymorphisms (SNPs) consistently occurred in every isolate; all were polymorphisms in open-reading frame (ORF) 62, and 2 confer amino acid substitutions in the immediate-early protein 62. Four wild-type SNPs occurred in every isolate: one each occurred in ORF 10, ORF 21, ORF 62, and a noncoding region upstream of ORF 64. The frequencies of the remaining wild-type SNPs were variable, with the SNPs uniformly expressed (even in mixtures) in 20.5%-97.4% of isolates (mean frequency, 67.7%). No 2 clinical isolates had identical SNP profiles; as such, vaccine latency usually involves >1 strain.
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The current status of live attenuated varicella vaccine (Gershon, A. A.) Evidence for frequent reactivation of the Oka varicella vaccine strain in healthy vaccines (Krause, P. R.) Investigation of varicella-zoster virus variation by heteroduplex mobility assay (Barrett-Muir, W., Hawrami, K., Clarke, J., Breuer, J.) Varicella-zoster virus with a lost gE epitope: evidence for immunological pressure by the human antibody response (Padilla, J. A., Grose, C.) Biologic and geographic differences between vaccine and clinical varicella-zoster virus isolates (LaRussa, P. S., Gershon, A. A.) Comparison of DNA sequence and transactivation activity of open reading frame 62 of Oka varicella vaccine and its parental viruses (Gomi, Y., Imagawa, T., Takahashi, M., Yamanishi, K.) Cis and trans elements regulating expression of the varicella-zoster virus gI gene (He, H., Boucaud, D., Hay, J., Ruyechan, W. T.) Interactions among structural proteins of varicella-zoster virus (Spengler, M., Niesen, N., Grose, C., Ruyechan, W. T., Hay, J.) The role of varicella-zoster virus immediate-early proteins in latency and their potential use as components of vaccines (Sadzot-Delvaux, C., Rentier, B.) Mutagenesis of the varicella-zoster virus genome: lessons learned (Cohen, J. I.) Immune evasion mechanisms of varicella-zoster virus (Abendroth, A., Arvin, A.) Pathway of viral spread in herpes zoster: detection of the protein encoded by open reading frame 63 of varicella-zoster virus in biopsy specimens (Iwasaki, T., Muraki, R., Kasahara, T., Sato, Y., Sata, T., Kurata, T.) Vaccination against cytomegalovirus (Plotkin, S. A.) Varicella-zoster virus in human and rat tissue specimens (Annunziato, P. W., Lungu, O., Panagiotidis, C.) In vitro measurement of human T cell responses to varicella-zoster virus antigen (Hayward, A. R.) Use of varicella vaccines to prevent herpes zoster in older individuals (Levin, M. J.) Immunization of the elderly to boost immunity against varicella-zoster virus (VZV) as assessed by VZV skin test reaction (Takahashi, M., Kamiya, H., Asano, Y., Shiraki, K., Baba, K., Otsuka, T., Hirota, T., Yamanishi, K.) Varicella-zoster virus immunity and prevention: a conference perspective (Straus, S. E.).
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The sequences of ∼34 kb from the 3′ end of the varicella-zoster virus (VZV) Oka vaccine strain and the previously sequenced Dumas strain were compared. Sequence differences were noted in the coding sequences of several VZV open reading frames (ORFs), including ORFs 48, 51, 52, 55, 56, 58, 59, 60, 62, 64, and 68. Tests based on differences in the ORF62 gene and in the ORF64 poly-A region successfully distinguished the Oka vaccine strain from its wild-type parent and from other Japanese and US clinical isolates. These changes remained stable after passage of the virus in humans.
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