Live Attenuated Varicella Vaccine: The KMcC Strain in Healthy Children

PEDIATRICS ◽  
1983 ◽  
Vol 71 (3) ◽  
pp. 307-312
Author(s):  
Allan M. Arbeter ◽  
Stuart E. Starr ◽  
Robert E. Weibel ◽  
Beverly J. Neff ◽  
Stanley A. Plotkin
Keyword(s):  
Varicella Zoster Virus ◽  
Lymphocyte Proliferation ◽  
Fluorescent Antibody ◽  
Varicella Vaccine ◽  
Skin Lesions ◽  
Healthy Children ◽  
Varicella Zoster ◽  
Immune Adherence ◽  
50Th Passage

The KMcC strain of live, attenuated varicella-zoster virus vaccine was studied in healthy children as a preliminary step toward varicella vaccine studies with this strain in children with leukemia. Forty-three children were immunized: 26 with the 40th passage vaccine and 17 with the 50th passage. Studies included surveillance for clinical reactivity, oropharyngeal excretion of vaccine virus, viruria, and viremia. Antibody responses were assayed by fluorescent antibody to membrance antigens and immune adherence hemagglutination. Cell-mediated immune responses were assayed by lymphocyte proliferation to varicella-zoster virus specific antigens. There was 100% seroconversion to the KMcC passage 40 and 50 vaccines (by fluorescent antibody to membrane antigen assay). Every child studied developed in vitro lymphocyte proliferation to varicella-zoster virus antigens. Papular skin lesions, probably vaccine related, occurred in 31% of the 40th passage vaccinees but in only 6% of the 50th passage vaccinees. The 50th passage KMcC strain vaccine is sufficiently immunogenic and safe to initiate clinical studies with leukemia patients.

Modified Chickenpox in Children Immunized With the Oka/Merck Varicella Vaccine

PEDIATRICS ◽  
1993 ◽  
Vol 91 (1) ◽  
pp. 17-22 ◽  
Author(s):  
Barbara M. Watson ◽  
Sharon A. Piercy ◽  
Stanley A. Plotkin ◽  
Stuart E. Starr
Keyword(s):  
Virus Infection ◽  
Varicella Zoster Virus ◽  
Median Time ◽  
Index Case ◽  
Varicella Vaccine ◽  
Skin Lesions ◽  
Varicella Zoster Virus Infection ◽  
Healthy Children ◽  
Varicella Zoster ◽  
Index Cases

Oka/Merck varicella vaccine has been studied in this institution since 1981. Persistence of antibody for 6 to 8 years has been demonstrated; however, cases of chickenpox have been seen in immunized children. The severity of chickenpox in healthy children who have received Oka/Merck varicella vaccine since 1981 is described. All vaccinees who developed chickenpox-like rashes more than 6 weeks postimmunization were exammined. Of 2163 vaccinees, 164 were examined, of whom 114 had rashes consistent with chickenpox. When sera were available (46%), antibody studies uniformly confirmed varicella-zoster virus infection. Chickenpox occurred 2 to 96 months (median of 44 months) postimmunization. The range for the number of skin lesions was 1 to 285 (median 18) in seroconverters. Symptoms included itching in 39%, fever in 9%, headaches in 7%, lymphadenopathy in 3%, and malaise in 2%; 54% were asymptomatic, except for the rash. The median time to total healing was 5 days. The median time lost from school was 2 days. Thirteen of the children in whom infections developed had failed to seroconvert after immunization. Their infections were similar in severity to those of children who had seroconverted originally. When varicella was introduced into families as a result of chickenpox in an immunized family member (index case), the rate of secondary chickenpox among immunized siblings was 12.2%. Eleven such secondary cases were similar in severity to the 9 index cases. It is concluded that chickenpox is generally mild in previously immunized children.

Varicella-Zoster Virus (Varicella and Shingles)

2021 ◽  
Author(s):  
Anne Gershon
Keyword(s):  
Varicella Zoster Virus ◽  
Varicella Vaccine ◽  
The United States ◽  
Primary Immune Response ◽  
Wild Type Virus ◽  
High Dose ◽  
Healthy Children ◽  
Zoster Vaccine ◽  
Live Attenuated Vaccine ◽  
Varicella Zoster

A live attenuated vaccine against varicella (later also used to prevent zoster) was developed in 1974 by Takahashi and colleagues. Varicella vaccine was licensed for universal immunization of healthy children in the United States in 1995. It is also now used for this purpose in at least 15 additional countries all over the world. Varicella is disappearing in the US. Varicella vaccine has proven extremely safe and side effects are unusual, mild, and less serious than varicella or its complications. 85% of children are protected completely after 1 dose; the 15% who develop varicella despite immunization usually (but not always) have mild infections. These 15%, however, can transmit the wild type virus to others. Therefore, for optimal effect, 2 doses are required, mostly to address children who did not have an optimal primary immune response after the first dose. Waning immunity does not seem to pose a serious problem, but surveillance of vaccinees is continuing. It was demonstrated in 2005 that at a high dose of vaccine – 15 times higher than that used for prevention of varicella in children - zoster in adults can also be safely prevented. The live attenuated zoster vaccine is effective in approximately 50% of healthy individuals over age 60 who have had varicella in the past, and therefore have latent infection with varicella-zoster virus. It is given as one dose, but its effect runs out about 8 years after vaccination. In 2017, a new vaccine against zoster was also introduced. This is a subunit vaccine which does not contain contagious virus. It is even more effective than the older zoster vaccine and is over 95% effective in adults 50–≥70 years of age in preventing zoster and post herpetic neuralgia.

Humoral Immunity and Clinical Reinfections Following Varicella Vaccine in Healthy Children

PEDIATRICS ◽  
1989 ◽  
Vol 84 (3) ◽  
pp. 418-421 ◽  
Author(s):  
Candice Johnson ◽  
Leonard P. Rome ◽  
Terry Stancin ◽  
Mary L. Kumar
Keyword(s):  
Repeated Measures ◽  
Fluorescent Antibody ◽  
Geometric Mean ◽  
Varicella Vaccine ◽  
Critical Issue ◽  
Healthy Children ◽  
Varicella Zoster ◽  
Antibody Persistence ◽  
The Difference ◽  
Post Hoc

The duration of immunity following vancella-zoster vaccination in healthy children remains a critical issue. In a 3-year study of 140 OKA/Merck vaccine recipients, duration of immunity was assessed by two measures. The first was persistence of varicellazoster antibody measured by modified fluorescent antibody to membrane antigen test. Thirty-six toddler vaccinees 12 to 24 months of age had sera obtained at 6 weeks, 1 year, and 2 years. Geometric mean titer ± SD at 6 weeks was 57.7 ± 2.9; at 1 year, it was 12.4 ± 3.9; at 2 years, it was 9.9 ± 3.9. Repeated-measures analysis of variance showed a significant overall decrease in antibody titer with time (F = 30.62, P < .001). Post hoc comparisons indicated that the 6-week and 1-year titers were significantly different (P < .001), but the difference between 1 and 2 years was not (P = .138). Clinical reinfections were also examined for 3 years after vaccination. Suspected varicella cases were confirmed by a fourfold or more increase in titer. Of 84 toddlers, 68 were exposed one or more times, and 6 became reinfected. Of 49 siblings, 45 were exposed, and one became reinfected. All 7 children had < 70 vesicles and 6 of 7 were afebrile. No cases of zoster occurred. It is concluded that OKA/Merck varicella-zoster vaccination leads to antibody persistence for 2 years and the few reinfections that do occur are greatly attenuated.

scholarly journals Detection of Antibodies to Varicella-Zoster Virus in Recipients of the Varicella Vaccine by Using a Luciferase Immunoprecipitation System Assay

2014 ◽  
Vol 21 (9) ◽  
pp. 1288-1291 ◽  
Author(s):  
Jeffrey I. Cohen ◽  
Mir A. Ali ◽  
Ahmad Bayat ◽  
Sharon P. Steinberg ◽  
Hosun Park ◽  
...  
Keyword(s):  
Varicella Zoster Virus ◽  
High Throughput ◽  
Fluorescent Antibody ◽  
Varicella Vaccine ◽  
The United States ◽  
Antibody Detection ◽  
Enzyme Linked Immunosorbent Assay ◽  
Viral Capsid Antigen ◽  
Glycoprotein E ◽  
Varicella Zoster

ABSTRACTA high-throughput test to detect varicella-zoster virus (VZV) antibodies in varicella vaccine recipients is not currently available. One of the most sensitive tests for detecting VZV antibodies after vaccination is the fluorescent antibody to membrane antigen (FAMA) test. Unfortunately, this test is labor-intensive, somewhat subjective to read, and not commercially available. Therefore, we developed a highly quantitative and high-throughput luciferase immunoprecipitation system (LIPS) assay to detect antibody to VZV glycoprotein E (gE). Tests of children who received the varicella vaccine showed that the gE LIPS assay had 90% sensitivity and 70% specificity, a viral capsid antigen enzyme-linked immunosorbent assay (ELISA) had 67% and 87% specificity, and a glycoprotein ELISA (not commercially available in the United States) had 94% sensitivity and 74% specificity compared with the FAMA test. The rates of antibody detection by the gE LIPS and glycoprotein ELISA were not statistically different. Therefore, the gE LIPS assay may be useful for detecting VZV antibodies in varicella vaccine recipients. (This study has been registered at ClinicalTrials.gov under registration no. NCT00921999.)

DNA sequence analysis of varicella-zoster virus gene 62 from subclinical infections in healthy children immunized with the Oka varicella vaccine

Vaccine ◽  
2008 ◽  
Vol 26 (44) ◽  
pp. 5627-5632 ◽  
Author(s):  
Yasuyuki Gomi ◽  
Takao Ozaki ◽  
Naoko Nishimura ◽  
Atsushi Narita ◽  
Michio Suzuki ◽  
...  
Keyword(s):  
Sequence Analysis ◽  
Varicella Zoster Virus ◽  
Dna Sequence ◽  
Varicella Vaccine ◽  
Dna Sequence Analysis ◽  
Healthy Children ◽  
Varicella Zoster ◽  
Virus Gene

scholarly journals Molecular Analysis of Varicella Vaccines and Varicella-Zoster Virus from Vaccine-Related Skin Lesions

2011 ◽  
Vol 18 (7) ◽  
pp. 1058-1066 ◽  
Author(s):  
Sonja Thiele ◽  
Aljona Borschewski ◽  
Judit Küchler ◽  
Marc Bieberbach ◽  
Sebastian Voigt ◽  
...  
Keyword(s):  
Varicella Zoster Virus ◽  
Varicella Vaccine ◽  
Developed Countries ◽  
Skin Lesions ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide ◽  
Reading Frame ◽  
Varicella Zoster ◽  
Core Set ◽  
Vaccine Type

ABSTRACTTo prevent complications that might follow an infection with varicella-zoster virus (VZV), the live attenuated Oka strain (V-Oka) is administered to children in many developed countries. Three vaccine brands (Varivax from Sanofi Pasteur MSD; Varilrix and Priorix-Tetra, both from Glaxo-Smith-Kline) are licensed in Germany and have been associated with both different degrees of vaccine effectiveness and adverse effects. To identify genetic variants in the vaccines that might contribute to rash-associated syndromes, single nucleotide polymorphism (SNP) profiles of variants from the three vaccines and rash-associated vaccine-type VZV from German vaccinees were quantitatively compared by PCR-based pyrosequencing (PSQ). The Varivax vaccine contained an estimated 3-fold higher diversity of VZV variants, with 20% more wild-type (wt) SNPs than Varilrix and Priorix-Tetra. These minor VZV variants in the vaccines were identified by analyzing cloned full-length open reading frame (ORF)orf62sequences by chain termination sequencing and PSQ. Some of these sequences amplified from vaccine VZV were very similar or identical to those of the rash-associated vaccine-type VZV from vaccinees and were almost exclusively detected in Varivax. Therefore, minorities of rash-associated VZV variants are present in varicella vaccine formulations, and it can be concluded that the analysis of a core set of four SNPs is required as a minimum for a firm diagnostic differentiation of vaccine-type VZV from wt VZV.

Varicella in Pediatric Patients

1993 ◽  
Vol 27 (7-8) ◽  
pp. 938-949 ◽  
Author(s):  
Laureen A. Drwal-Klein ◽  
Carmel A. O'Donovan
Keyword(s):  
Varicella Zoster Virus ◽  
Antiviral Therapy ◽  
Pediatric Patients ◽  
Pediatric Population ◽  
Varicella Vaccine ◽  
Clinical Manifestations ◽  
Search Term ◽  
Healthy Children ◽  
Varicella Zoster ◽  
Treatment And Prevention

OBJECTIVE: To summarize the literature describing the epidemiology, transmission, clinical manifestations, diagnosis, treatment, and prevention of varicella in the pediatric population. DATA SOURCES: A literature search of English-language articles from 1982 to 1992 using MEDLINE and bibliographies of relevant articles. The search term used was varicella. STUDY SELECTION: All review articles and original studies addressing the epidemiology, transmission, clinical manifestations, complications, diagnosis, treatment, and prevention of varicella in pediatric patients were reviewed. Emphasis was placed on controlled studies done in the US. DATA EXTRACTION: Data from human studies were extracted by the authors and evaluated according to patient population, sample size, dosing regimen, efficacy, and safety. DATA SYNTHESIS: Varicella-zoster virus is a highly contagious virus that produces a common and costly disease in the pediatric population. The primary manifestation of varicella is the eruption of vesicular lesions. In most cases varicella is benign, but it can be associated with serious complications. Diagnosis is based primarily on clinical findings. Otherwise healthy children have traditionally received only symptomatic treatment for varicella, but recent literature suggests that antiviral therapy may be useful in these patients. Immunocompromised patients benefit from both symptomatic and antiviral therapy. Isolation and varicella-zoster immune globulin are used to prevent varicella. In the future, varicella vaccine will play an important role in preventing the disease. Varicella vaccine has been shown to be immunogenic and clinically effective in both healthy and immunocompromised children. Adverse reactions associated with the vaccine include fever, injection-site reactions, and rash. Although zoster can follow vaccination, the incidence appears to be lower in vaccinated individuals. Preliminary studies have shown that the vaccine provides protection from varicella-zoster virus for an extended period of time. CONCLUSIONS: Varicella is a common, usually benign disease of childhood. All patients may benefit from symptomatic therapy. Current literature does not support the use of antiviral therapy in all pediatric patients with varicella. When commercially available, varicella vaccine will play an important role in prevention. Long-term studies are needed to fully assess the risk of developing varicella and zoster following vaccination.

Varicella-Zoster Virus

2018 ◽  
Author(s):  
Olivier Picone ◽  
Christelle Vauloup-Fellous ◽  
Laurent Mandelbrot
Keyword(s):  
Varicella Zoster Virus ◽  
Early Recognition ◽  
Varicella Vaccine ◽  
Skin Lesions ◽  
Varicella Infection ◽  
Varicella Zoster ◽  
Mother And Child ◽  
Life Threatening ◽  
Peripartum Period ◽  
The Impact

Chickenpox in a pregnant woman is uncommon, but it is a major concern for patients and their families, as well as for clinicians caring for pregnant women. Varicella infection during pregnancy is usually benign, but there can be serious consequences for both mother and child. Notably, fetal varicella syndrome (FVS) can happen when infection occurs before 21 weeks of gestation. It can present with serious neurological anomalies and unusual cicatricial skin lesions. Later in pregnancy, primary neonatal varicella may occur when the mother is infected in the peripartum period, and it can be life-threatening. The complications of varicella during pregnancy are reviewed, with an emphasis on early recognition, accurate timing of infection, and risk to the developing fetus and newborn infant. The impact of varicella vaccine on the epidemiology of these infections is reviewed, as well as indications for varicella-zoster virus (VZV)–specific immune globulin and antiviral therapy with acyclovir.

scholarly journals A unique spliced varicella-zoster virus latency transcript represses expression of the viral transactivator gene 61

2017 ◽  
Author(s):  
Daniel P. Depledge ◽  
Werner J. D. Ouwendijk ◽  
Tomohiko Sadaoka ◽  
Shirley E. Braspenning ◽  
Yasuko Mori ◽  
...  
Keyword(s):  
Varicella Zoster Virus ◽  
Functional Characterization ◽  
Skin Lesions ◽  
Reading Frame ◽  
Varicella Zoster ◽  
Viral Transactivator ◽  
Virus Latency ◽  
Latently Infected ◽  
Alternatively Spliced

During primary infection, neurotropic alphaherpesviruses (αHVs) gain access to neurons in sensory and cranial ganglia establishing lifelong latent infection from which they can later reactivate to cause debilitating disease1. For most αHVs, including the best-studied herpes simplex type 1 ( HSV-1), viral latency is characterized by expression of a single or restricted set of transcripts that map antisense to the open reading frame (ORF) homologous to the major HSV immediate early viral transactivator, ICP02. These latency transcripts, either directly or through encoded miRNAs or proteins, repress expression of the ICP0 orthologues3–5. The exception is varicella-zoster virus (VZV), an αHV which infects over 90% of adults and for which neither a canonical latency transcript1,6–8 nor a putative mechanism for repressing lytic transcription during latency have been identified. Here, we describe the discovery and functional characterization of a VZV latency transcript (VLT), that maps antisense to VZV ORF 61 (the VZV ICP0 homologue9,10), and which is consistently expressed in neurons of latently infected human trigeminal ganglia (TG). VLT encodes a protein with late kinetics during lytic VZV infection in vitro and in zoster skin lesions. Whereas multiple alternatively spliced VLT isoforms are expressed during lytic VZV infection, a single unique VLT isoform that specifically suppresses ORF61 gene expression predominates in latently VZV-infected human TG. The discovery of VLT directly unifies the latent VZV transcription program with those of better-characterized αHVs, removing longstanding barriers to understanding VZV latency and paving the way for research into the development of vaccines that do not establish latency or reactivate, and drugs that eradicate latent VZV.

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