Attenuated Varicella Vaccine Research Articles

Immunogenicity and safety of a live attenuated varicella vaccine in children aged 1 to 12 years: A double-blind, randomized, parallel-controlled phase III clinical trial in China

ABSTRACT Chickenpox outbreaks frequently occur in collective settings such as kindergartens and schools, posing a significant threat to children’s physical and mental health. This study aimed to evaluate the immunogenicity and safety of the freeze-dried live attenuated varicella vaccine (VarV) developed by Beijing Minhai Biotechnology Co. LTD. in healthy participants aged 1–12 years. In this phase III, single-center, randomized, double-blind, active-controlled trial,1,200 healthy participants randomly assigned in a 1:1 ratio to receive one dose of either the test vaccine or the active control vaccine. Venous blood samples were collected before vaccination and 42 days after vaccination, and the fluorescent antibody to membrane antigen (FAMA) assay was used to detect VZV antibody. Adverse events (AEs) observed within 42 days after vaccination and serious adverse events (SAEs) within six months after vaccination were recorded. The seroconversion rates in the test and control groups were 96.79% and 96.43%, respectively, with a difference of 0.36% (95% CI, −1.76%–2.48%). The geometric mean titers (GMTs) were 61.74 and 58.04, respectively, with a difference of 1.06 (95% CI, 0.92–1.23). The lower limits of the 95% CI for the differences in seroconversion rates and GMT ratios between the two groups were greater than their respective pre-set non-inferiority margins. The overall incidence of AEs (p = .0112) in the test group was significantly lower than that in the control group. The freeze-dried live attenuated VarV developed by Beijing Minhai Biotechnology Co. LTD. demonstrated good immunogenicity and higher safety compared to the active control vaccine in healthy participants aged 1–12 years.

Pediatric Varicella-related Hospitalization in Turkey Between 2008 and 2018: Impact of Universal Single Dose Varicella Vaccine (VARICOMP Study).

A single-dose varicella vaccine at 12 months of age was introduced to the National Immunization Program in February 2013 in Turkey. This study aimed to evaluate varicella-related hospitalization in children and the impact of a single-dose live attenuated varicella vaccine over the first 5.5 years of introducing a universal varicella vaccination. We analyzed data collected from the medical records of children <18 years old who required hospitalization due to varicella in 17 cities representing 50% of the childhood population in Turkey between 2008 and 2018. We calculated the rate of hospitalization for varicella per 100,000 children during the study period. The main objective of this study was to determine the yearly rate of hospitalization due to varicella and to compare these rates in the pre-vaccine and post-vaccine periods. The secondary objective was to compare demographic features, varicella-related complications, and outcomes between the pre-vaccine and post-vaccine periods. A total of 4373 children (2458 boys and 1915 girls; 72.3% previously healthy) were hospitalized for varicella over a 10-year period, including 2139 children during the pre-vaccine period and 2234 children during the post-vaccine period. Overall, varicella hospitalization rates decreased significantly after the introduction of varicella vaccination [pre-vaccine vs. post-vaccine period; 3.79 vs. 2.87 per 100,000 per year; P < 0.001; odds ratio 0.75; 95% confidence interval 0.64-0.88]. The incidence of varicella-related hospitalization among children between 1 and 5 years of age was significantly lower in the post-vaccine era than in the pre-vaccine era, with a 60.2% decrease in hospitalizations (2.43 vs. 6.12 per 100,000 children; P < 0.001, odds ratio 0.39; 95% confidence interval 0.34-0.46). In both the <1-year and 6- to 10-year age groups, the incidence of varicella-related hospitalizations was similar in the pre-vaccine and post-vaccine periods. The incidence of varicella-related hospitalization was higher in the post-vaccine era among 11-15 years and >15-year-old groups ( P < 0.01 and P < 0.05). The mean age was higher during the post-vaccine period than during the pre-vaccine period ( P < 0.001). The absolute number of secondary bacterial infections ( P < 0.01), respiratory complications ( P < 0.01), and neurological complications ( P < 0.001) was significantly lower during the post-vaccine period. The incidence of severe varicella was lower during the post-vaccine period than during the pre-vaccine period ( P < 0.001). After 5.5 years of routine single-dose varicella vaccine use, we observed the impact of varicella vaccination on the incidence of varicella-related hospitalizations, especially in the target age group. However, we did not observe herd protection in the other age groups. The implementation of a second dose of the varicella vaccine in the National Immunization Program would help control disease activity.

Preliminary investigation and analysis of nucleotide site variability of nine glycoproteins on varicella-zoster virus envelope, Jilin Province, China, 2010-March 2024

Varicella is endemic worldwide. In China, varicella has not yet been included in the list of legal infectious diseases, nor has a unified national surveillance program been established. And the live attenuated varicella vaccine has not been included in routine immunization. In this study, we analyzed for the first time the varicella epidemiology in Jilin Province in the past 20 years, and the nucleotide site, amino acid site and N-glycosylation site variation of glycoprotein in varicella-zoster virus (VZV) surface 9 in the past 15 years. The results showed that the reported incidence of varicella in Jilin Province in the last 20 years was fluctuating above and below 20/100,000, especially after the epidemic of the COVID-19, and fatal cases appeared in individual years. The genotypic branching of VZV was monitored as Clade 2 in the last 15 years. 9 glycogen nucleotide sites of VZV had different degrees of variability, and the variability had specificity. Therefore, it gives us the idea that in order to reduce the incidence of varicella and herpes zoster, a provincial or even national surveillance program should be introduced as early as possible, and the dynamic monitoring of the variability of the nucleotide sites of VZV should be strengthened at the same time as the vaccine immunization strategy is introduced.

The impact of the implementation of the two-dose varicella vaccine immunization strategy in Quzhou: A retrospective birth cohort study

ABSTRACT Varicella is a vaccine-preventable disease caused by the varicella zoster virus (VZV), but the varicella incidence among children has increased in recent years. This was a retrospective birth cohort study based on the Zhejiang Provincial Immune Information System (ZJIIS) and the China Information System for Disease Control and Prevention (CISDCP) in Quzhou. A total of 1,291 clinically diagnosed varicella cases born from 2009 to 2014 were collected during 2009–2023, which were analyzed the impact of changes in vaccination strategy on the incidence of varicella based on the Cox-proportional hazards model. It was observed that the onset age of varicella shifted to the older age group and later to 9–11 years. After the change to the two-dose varicella vaccination strategy, the population affected by varicella was concentrated among students and received more than one dose of live attenuated varicella vaccine (VarV). Based on the Coxproportional hazards model and adjusting for all covariates, the risk of varicella infection in children decreased after the introduction of the two-dose varicella vaccination strategy (HR = 0.04, 95% CI: 0.03–0.05). Meanwhile, the Kaplan–Meier curves also showed that the hazards were lower after the change in vaccination strategy. It is recommended that two doses of VarV should be included in the national immunization schedule and that full vaccination should be completed approximately four years after the first dose.

Glycoprotein E-Displaying Nanoparticles Induce Robust Neutralizing Antibodies and T-Cell Response against Varicella Zoster Virus.

The Varicella zoster virus (VZV), responsible for both varicella (chickenpox) and herpes zoster (shingles), presents significant global health challenges. While primary VZV infection primarily affects children, leading to chickenpox, reactivation in later life can result in herpes zoster and associated post-herpetic neuralgia, among other complications. Vaccination remains the most effective strategy for VZV prevention, with current vaccines largely based on the attenuated vOka strains. Although these vaccines are generally effective, they can induce varicella-like rashes and have sparked concerns regarding cell virulence. As a safer alternative, subunit vaccines circumvent these issues. In this study, we developed a nanoparticle-based vaccine displaying the glycoprotein E (gE) on ferritin particles using the SpyCatcher/SpyTag system, termed FR-gE. This FR-gE nanoparticle antigen elicited substantial gE-specific binding and VZV-neutralizing antibody responses in BALB/c and C57BL/6 mice-responses that were up to 3.2-fold greater than those elicited by the subunit gE while formulated with FH002C, aluminum hydroxide, or a liposome-based XUA01 adjuvant. Antibody subclass analysis revealed that FR-gE produced comparable levels of IgG1 and significantly higher levels of IgG2a compared to subunit gE, indicating a Th1-biased immune response. Notably, XUA01-adjuvanted FR-gE induced a significant increase in neutralizing antibody response compared to the live attenuated varicella vaccine and recombinant vaccine, Shingrix. Furthermore, ELISPOT assays demonstrated that immunization with FR-gE/XUA01 generated IFN-γ and IL-2 levels comparable to those induced by Shingrix. These findings underscore the potential of FR-gE as a promising immunogen for the development of varicella and herpes zoster vaccines.

Exploring Varicella Vaccine Coverage and Influencing Factors in Rural and Pastoral Children of Qinghai Province: A Cross-Sectional Catch-Up Vaccination Study

&amp;lt;i&amp;gt;Background: &amp;lt;/i&amp;gt;Varicella is a respiratory infectious disease caused by varicella-zoster virus (VZV) infection. Varicella vaccine has been shown to be highly effective in preventing varicella disease, however it is not included in Qinghai Province’s local immunization planning program and must be paid for by families. Its use in local areas is options instead of compulsory, so high coverage is difficult to guarantee. Starting in October 2021, one dose of live attenuated varicella vaccine was recommended at lest for 3-17-year-old children in Qinghai. In 2022, it was conducted that an investigation of varicella vaccine coverage and factors influencing coverage among children in rural rural and pastoral areas to determine the impact of this VarV catch-up policy. &amp;lt;i&amp;gt;Objective: &amp;lt;/i&amp;gt; To explore varicella vaccine coverage and factors influencing caverage among 3-17-year-old children in rural and pastoral areas of Qinghai province. &amp;lt;i&amp;gt;Methods:&amp;lt;/i&amp;gt; A stratified cluster sampling method was used to select children aged 3-17 years from kindergartens and primary /secondary schools in rural and pastoral areas of Qinghai province for a questionnaire-based survey of their guardians. Coverage levels of one and two doses of VarV (VarV&amp;lt;sub&amp;gt;1&amp;lt;/sub&amp;gt; and VarV&amp;lt;sub&amp;gt;2&amp;lt;/sub&amp;gt;) before and after a catch-up vaccination activity initiated in October 2021, and identified factors influenceing VarV&amp;lt;sub&amp;gt;1&amp;lt;/sub&amp;gt; coverage. &amp;lt;i&amp;gt;Results:&amp;lt;/i&amp;gt; VarV&amp;lt;sub&amp;gt;1&amp;lt;/sub&amp;gt; and VarV&amp;lt;sub&amp;gt;2 &amp;lt;/sub&amp;gt;coverage levels after the catch-up activity were 79.06% (676/855) and 43.79% (363/829), respectively, and increased by 34.38 and 24.13 percentage points compared with before the catch-up activity. Multivariate logistic regression showed that VarV&amp;lt;sub&amp;gt;1 &amp;lt;/sub&amp;gt;coverage was higher in rural areas than in pastoral areas (OR=4.63, 95%&amp;lt;I&amp;gt;CI&amp;lt;/I&amp;gt;: 2.91-7.39), and higher among children whose guardians scored 4-6 or 7-10 points on knowledge about varicella and VarV than among children whose guardians scored 0-3 points (OR=8.61, 95%&amp;lt;I&amp;gt;CI&amp;lt;/I&amp;gt;: 4.73-15.69, OR=2.86, 95%&amp;lt;I&amp;gt;CI&amp;lt;/I&amp;gt;: 1.69-4.84). the main reasons for non-vaccination were guardians’ lack of understanding of VarV (48.6%, 87 children), guardians’ unawarness of the need for VarV vaccination (43.6%, 78 children), and unavailability of VarV at vaccination centers (31.3%, 56 children). &amp;lt;i&amp;gt;Conclusions: &amp;lt;/i&amp;gt;The catch-up activity significantly increased VarV coverage among children in the surveyed areas. It should been strengthened that health education on knowledge about varicella and VarV among guardians of children in Qinghai, especially in pastoral areas, to promote VarV vaccination of age-eligible children.

Heightened incidence of adverse events associated with a live attenuated varicella vaccine strain that lacks critical genetic polymorphisms in open reading frame 62

This study aimed to identify the specific vaccine strain associated with herpes zoster (HZ) in children following a series of diagnosed cases and to explore whether differences in single nucleotide polymorphisms (SNPs) among various vaccine strains are linked to an increased incidence of herpes zoster after vaccination. From February 2021 to March 2024, children <12years old suspected of vaccine-related varicella-like rash or HZ were included. Varicella zoster virus DNA isolated from the patients were sequenced to differentiate vaccine type versus wild-type. 3D protein structures of pORF62 were simulated using open reading frame 62 sequences extracted from whole genome sequencing of vOka, MAV/06, Oka/SK vaccines, and pOka reference. A total of 27 children with a median age of 2.1 (interquartile range, 1.5-3.4) years old presented with vaccine-related varicella-like rash (n=4/27, 14.8%) or HZ (n=23/27, 85.2%). One patient with varicella-like rash and 34.8% (n=8/23) with HZ had disseminated skin involvement. All were immunized with the Oka/SK strain varicella vaccine. Genotyping showed 88.2% (n=15/17) had SNPs specific to the Oka/SK strain, and two had SNPs considered pOka type contained within the Oka/SK vaccine. Despite accumulations of SNPs in ORF 62 of Oka/SK, the translated amino acid sequence and 3D protein structure were identical to wild-type pOka's pORF62. In vOKA and MAV/06, changes in amino acids occurred at two positions, S628G and R958G, within pORF62. The predicted 3D protein structure of vOka and MAV/06's pORF62 showed that the α helical structure within region I undergoes conformational change, potentially increasing difficulties in interactions with infection-related proteins and thereby decreasing virulence. pORF62 in pOka and Oka/SK exhibited more stable structure complex of the α helical structure. Lack of structural alternations in region I of pORF62 due to the absence of critical genetic polymorphisms in open reading frame 62 could be associated with the heightened incidence of adverse events.

Analysis of the implementation effect and evaluation of the vaccine protection effect of the live attenuated varicella vaccine program for school-age children in Bao’an district of Shenzhen,China

ABSTRACT The objective of the study is to analyze the implementation effect of the Live Attenuated Varicella Vaccine (VarV) Vaccination Program for eligible children in Bao’an District, Shenzhen, and evaluate the vaccine effectiveness. Children’s vaccination data was obtained from the Shenzhen Immunization Planning Information Management System, while varicella case data came from the China Disease Prevention and Control Information System. The Joinpoint regression method examined vaccination rate trends, and a retrospective cohort study assessed vaccine effectiveness. After program implementation, VarV vaccination rates significantly increased, surpassing provincial and national averages. Overall incidence declined 54.6% across age groups, with the largest reductions among 7- and 6-year-olds. One year post-vaccination, single-dose vaccine effectiveness was 91.1% (95% CI: 79.2% to 96.2%). However, two doses remained 91.4% effective(95% CI: 89.1% to 93.2%) after 7 years. Overall, Shenzhen’s VarV program achieved positive results. For children under six, routine immunization with two doses of VarV should be strengthened. Furthermore, we recommend that physicians conduct thorough inquiries to ascertain patients’ vaccination history and previous varicella infections. This will enable doctors to provide tailored vaccination recommendations based on comprehensive, practical evaluations.

Safety and Immunogenicity of the Live Attenuated Varicella Vaccine in Vietnamese Children Aged 12 Months to 12 Years: An Open-Label, Single-Arm Bridging Study.

This study aims to evaluate the safety and immunogenicity of the SKYVaricella vaccine in healthy Vietnamese children aged 12 months to 12 years. This open-label, single-arm study involved 201 children divided into two groups: 60 children aged 12 months to 5 years and 141 children aged 6 to 12 years. Safety was assessed through immediate reactions, solicited adverse events within 7 days, and unsolicited events up to Day 42. Immunogenicity was evaluated by seroconversion rates (SCR) and geometric mean titer (GMT) increments using fluorescent antibody-to-membrane antigen (FAMA) on the day of vaccination (D0) and 42 days after vaccination (D42). All participants completed the follow-up. Immediate adverse events included pain (8.0%), redness (8.0%), and swelling (20.9%) at the injection site. Within 7 days, pain (17.9%) and swelling (12.4%) were mild and self-resolving. Unsolicited adverse events were infrequent and mild. Both age groups achieved 100% SCR. GMT of varicella-zoster virus antibodies increased from 1.37 (SD 1.97) at D0 to 18.02 (SD 2.22) at D42, a 13.12-fold rise. No Grade 3 adverse events were observed. The SKYVaricella vaccine shows a robust immunogenic response and favorable safety profile in Vietnamese children aged 12 months to 12 years. These findings endorse its potential inclusion in pediatric vaccination programs as a reliable preventive option against varicella.

Development of potentiometric immunosensor for determination of live attenuated Varicella Vaccine: Potency and stability studies

Determination of Varicella vaccine's potency; containing live attenuated strain (Oka) of Varicella Zoster virus, has been limited to in vitro cell culture methods. In this study, a label free potentiometric biosensor has been developed for the first time and optimized to determine the content of varicella zoster virus. A passive ion-flux sensing platform has been developed using an anti-varicella monoclonal antibody and tetrabutyl ammonium bromide as a marker ion. The immunosensor has been optimized with respect to membrane diameter and concentration of the immobilized antibody. Linearity was achieved over a concentration range of 2.5-3.2 log PFU/dose with a LOD of 1.9 log PFU/dose. Potentiometric results were compared to the plaque-forming assay using the cell culture technique. The developed immunosensor was superior with respect to analysis time and cost without affecting critical analytical performance characteristics. Furthermore, in order to evaluate the stability indicating ability of the immunosensor, the effect of pH and temperature was investigated. Vaccine samples were subjected to forced degradation conditions; pH and elevated temperatures. Stability results showed the ability of immunosensor to differentiate between intact and degraded viral content. This would demonstrate the reliability of the immunosensor for evaluating the efficacy and stability of the vaccine.

Parent and healthcare provider views of live varicella vaccination of pediatric solid organ transplant recipients.

Live attenuated varicella vaccine (LAVV) has historically been contraindicated in children who are immunocompromised due to solid organ transplant (SOT) because of safety concerns. Recently, clinical guidelines were developed that support post-transplant varicella vaccination in selected SOT recipients based on emerging evidence of LAVV safety. This qualitative study sought to explore barriers and facilitators to implementing the new guidelines, as well as acceptability of LAVV among healthcare providers (HCPs) and parents. HCPs and parents of transplant recipients were recruited from four sites using purposive sampling. Data from semi-structured interviews were analyzed using an Interpretive Description approach that incorporated data from the interviews, academic knowledge and clinical experience, and drew from Grounded Theory and Thematic Analysis. The theoretical framework used was Adaptive Leadership. Thirty-four participants (16 HCPs and 18 parents) were included in the analysis. Parents developed skills in adaptive leadership that included strategies to protect their child against infectious diseases. Foundational information that live vaccines were absolutely contraindicated post-transplant "stuck" with parents and led them to develop strategies other than vaccination to keep their child safe. Some parents struggled to understand that information previously presented as a certainty (contraindication of LAVV) could change. Their approach to adaptive leadership informed their appraisal of the new vaccination guidelines and willingness to accept vaccination. HCPs should adopt a family-centered approach to communicating changing guidelines that considers parents' approach to adaptive leadership and discusses the changing nature of medical evidence. Trust between HCPs and parents can facilitate these conversations.

Safety of Interchanging the Live Attenuated MAV/06 Strain and OKA Strain Varicella Vaccines in Children.

Two live attenuated varicella vaccine (VZV) strains have been mainly used across the globe: MAV/06 and OKA strains. We aimed to explore the safety of interchanging the two VZV strains for primary and booster immunizations. South Korea's vaccine adverse event reporting system (VAERS) was accessed and searched to find filed reports of all adverse events (AEs) following immunization with the second dose of the varicella vaccine. The electronic medical records were reviewed for all visits to the hospital following the second dose of the varicella vaccine. Of the total 406 study participants, 27.5% (n = 112) were in the MAV/06-MAV/06 group, 30.3% (n = 123) in the MAV/06-OKA, 17.5% (n = 71) in the OKA-MAV/06 group, and 24.6% (n = 100) in the OKA-OKA group. Mean age at immunization with the first dose was 1.10 (standard deviation [SD] ±0.34) years old, and second dose was 4.77 (SD ± 1.13) (p = 0.772 and 0.933, respectively). There were no filed reports of AEs following the second dose in the national VAERS. Hospital visit records showed a total of 10.3% (95% confidence interval [CI], 7.6-13.7) (n = 42) had recorded AEs following the 2nd administered dose; however, only 0.7% (95% CI, 0.2-2.4) (n = 3) were regarded as possibly vaccine related. Two patients in the MAV/06-OKA group were diagnosed with Henoch-Schonlein purpura after the second dose; however, both had also received the MMR vaccine on the same day. No safety signals associated with interchanging the MAV/06 and OKA strain live attenuated varicella vaccines were observed in this patient cohort of healthy children.

Immunogenicity and Safety of a Newly Developed Live Attenuated Varicella Vaccine in Healthy Children: A Multi-National, Randomized, Double-Blinded, Active-Controlled, Phase 3 Study.

Korean manufacturers have developed a new varicella vaccine, NBP608. This phase 3, randomized, double-blind, multicenter study aimed to compare the immunogenicity and safety of NBP608 in healthy children to those of VarivaxTM (control). Children aged 12 months to 12 years were randomized in a ratio of 1:1 to receive either NBP608 or the control vaccine. Serum samples were obtained before vaccination and within six to eight weeks after vaccination. In total, 499 participants (NBP608, n = 251; control, n = 248) were enrolled. The seroconversion rate (SCR) measured using a FAMA assay was 99.53% in the NBP608 group, and the lower limit of the 95% confidence interval (95% LCL) for the SCR difference (NBP608 minus the control) was 0.52%. This 95% LCL for the difference was higher than the specified non-inferiority margin of -15%. In an assessment using gpELISA, the SCR was 99.53% in the NBP608 group, and the 95% LCL for the SCR difference was 6.5%, which was higher than the specified non-inferiority margin of -15%. There were no significant differences between the NBP608 and control group with respect to the proportions of participants who demonstrated local and systemic solicited AEs. This study indicated that NBP608 had a clinically acceptable safety profile and was not immunologically inferior to VarivaxTM.

Seroprevalence of varicella-zoster virus antibody and immunogenicity of live attenuated varicella vaccine in healthcare workers in Taiwan.

Healthcare workers (HCWs) without evidence of immunity to varicella-zoster virus (VZV) are recommended to undergo varicella vaccination. Immunogenicity of live attenuated varicella vaccine has rarely been investigated among HCWs in Taiwan. Anti-VZV immunoglobulin G (IgG) titer was checked for all HCWs at Changhua Christian Hospital from 2011 to 2017. One-dose and two-dose (separated by 4-8 weeks) vaccines were administered to HCWs with equivocal and negative anti-varicella IgG results, respectively. Follow-up anti-VZV IgG was determined at least 4 weeks after completion of vaccination. Factors associated with seroconversion to varicella vaccination were analyzed. Among 2406 included HCWs, the anti-VZV IgG serostatus was tested positive, equivocal and negative in 1924 (79.9%), 117 (4.9%) and 365 (15.2%), respectively. The seroprevalence had decreased from 88.0% (235/267) in 2011 to 72.2% (270/374) in 2017 (p for trend <0.05). A total of 67.8% (327/482) HCWs completed scheduled vaccination and serological follow-up. The seroconversion rates for HCWs with baseline equivocal and negative anti-VZV IgG results were 100% (80/80) and 79.4% (196/247) after one- and two-dose vaccination, respectively. In multivariate analysis, obesity (adjusted odds ratio, 0.308; 95% confidence interval [CI], 0.11-0.94, p=0.039) was the only factor statistically significantly associated with seroconversion to vaccination. Decreasing trends of seroprevalence of VZV were observed among HCWs from 2011 to 2017. HCWs who were obese were less likely to respond to varicella vaccination.

Vaccine Induced Herpes Zoster in An Immunocompetent Child After 3 months of 1st Dose of Vaccination

Varicella zoster virus (VZV) is an enveloped double stranded linear virus, which belongs to the herpesvirus’s family. It can cause two clinically different forms of diseases, primary infection known as chicken pox and latent infection know as herpes zoster (Shingles). Primary infection presents with diffuse vesicular rash accompanied by fever, malaise, and pharyngitis. However, latent infection results from reactivation of dormant virus in an immunocompromised patient and presents with painful localized skin rashes called as shingles. Currently, in the US, 2 doses of live attenuated varicella vaccine are available to prevent VZV infection. One of the major side effects of vaccination are the rashes. We report a unique case of vaccine induced VZV infection in a previously healthy child that presents with vesicular rashes 3 months after 1st dose of vaccination. A 16-month-old child with past medical history of premature birth at 32 weeks, presented to the pediatric outpatient clinic with complains of well-demarcated, erythematous, dry rash on both labia. Parents denied fever, cough, or any other signs and symptoms associated with rashes. patient activity level was normal and oral intake was usual. PCR testing was performed was found to be negative for Herpes Simplex Virus-1 (HSV-1) and Herpes Simplex Virus-2 (HSV-2) and positive for VZV. Due to patient recent vaccination status, further classification of infection was needed to determine if the source of infection was wild type chicken pox or vaccine induced. A swab of one of the vesicular lesions was sent to the Ohio Department of Health, for vaccine vs wild-type strain PCR testing. The results were positive for Vaccine induced VZV infection. The patient was started on acyclovir therapy. On follow-up, the patient condition improved clinically. In pediatric populations, it is important to do extensive evaluation of rashes post vaccination as it can be occurred due to wild type, break through or it can be vaccine induced virus. Proper evaluation can significantly impact the management patients as they are maybe infectious and need to be isolated in wild type and breakthrough infection versus non-infectious in case of vaccine induced. After detailed clinical history and physical examination, it is important to investigate further through PCR testing to differentiate one category from another!

342 A case series of live attenuated vaccine administration in dupilumab-treated children with atopic dermatitis

Abstract In patients with atopic dermatitis (AD), it is unknown whether suppression of dysregulated type 2 immune cytokines, interleukin-4 and interleukin-13, with dupilumab impacts the risk of viral infections following live attenuated vaccination. Current medical consensus and regulatory labelling recommend completing age-appropriate non-live vaccinations according to immunization guidelines at least 4 weeks prior to starting dupilumab and to avoid the use of live vaccines in patients treated with dupilumab. Phase 3 dupilumab AD clinical trial protocols prohibited the administration of live attenuated vaccines within 4 weeks before the baseline visit and during treatment. For patients in the LIBERTY AD PED open-label extension (OLE; NCT02612454) who required a live attenuated vaccine, the protocol specified that the study drug be discontinued for 12 weeks prior to planned administration and could be re-initiated 4 weeks after vaccine administration. However, one patient in the 16-week LIBERTY AD PRESCHOOL (NCT03346434, part B) study received a live attenuated vaccine with a ≤ 12 weeks gap between dupilumab administration and vaccination and eight patients in the LIBERTY AD PED-OLE received a live attenuated vaccine, four patients were vaccinated with a ≤ 12 weeks gap and four patients &amp;gt; 12 weeks after discontinuing dupilumab. To describe the clinical course of children with moderate-to-severe AD administered a live attenuated vaccine during the LIBERTY AD PRESCHOOL or LIBERTY AD PED-OLE study. Paediatric patients with moderate-to-severe AD who had previously participated in the phase 2 open-label, multicentre, sequential study LIBERTY AD PRESCHOOL (part A; 3 or 6 mg/kg dupilumab single dose) or the randomized, double-blind placebo-controlled phase 3 study LIBERTY AD PRESCHOOL (part B; 200 mg dupilumab every 4 weeks [q4w] if baseline weight 5 to &amp;lt;15 kg, or 300 mg q4w if 15 to &amp;lt;30 kg) were subsequently enrolled into the LIBERTY AD PED-OLE study (200 mg dupilumab q4w if baseline weight 5 to &amp;lt;15 kg, 300 mg q4w if 15 to &amp;lt;30 kg, or 200 mg q2w if 30 to &amp;lt;60 kg). This case series includes nine patients with severe AD at the parent study baseline (Investigator’s Global Assessment score = 4) and Peak Pruritus Numerical Rating Scale (range: 0–10) scores of 5.2 (n = 1), 8 (n = 2), 9 (n = 4) or 10 (n = 2), who were administered a live attenuated vaccine, with or without pause, during dupilumab treatment in the LIBERTY AD PRESCHOOL (part B; n = 1) or LIBERTY AD PED-OLE study (n = 8). Of the nine patients in this case series, eight were male. All were first diagnosed with AD between 0 and 6 months of age and age at enrolment varied from 8 to 56 months old. Dupilumab treatment duration up to the date of vaccination with live attenuated measles, mumps, rubella (MMR) and varicella vaccines (n = 5) or MMR vaccine only (n = 4) ranged from 85 to 840 days. No adverse events (AEs), including serious AEs, treatment-emergent infections and infestations, or serious infections were observed in the 4-week window post-vaccination. In this limited prospective case series of children with moderate-to-severe AD who also received the live attenuated MMR vaccine, with or without live attenuated varicella vaccine, no serious adverse events were observed within 4 weeks or after 4 weeks post-vaccination. Additional research is needed to assess the safety of live attenuated vaccines in patients on dupilumab treatment and to investigate whether dupilumab treatment impacts vaccine efficacy.

Immunogenicity and safety of a live attenuated varicella vaccine co-administered with inactive hepatitis A vaccine: A phase 4, single-center, randomized, controlled trial

ABSTRACT Co-administration of vaccines can facilitate the introduction of new vaccines in immunization schedules. This study aimed to evaluate the immunogenicity and safety of co-administration with live attenuated varicella vaccine (VarV) and inactivated hepatitis A vaccine (HepA) among children aged 12 ~ 15 months. In this phase 4 clinical trial, 450 children were randomized with a ratio of 1:1 to receive VarV and Hep A simultaneously (Group A) or separately (Group B). The primary endpoints were the seroconversion rate of anti-varicella-zoster virus (VZV) antibodies 42 days after vaccination of VarV and the seroconversion rate of anti-Hepatitis A virus (HAV) antibodies 30 days after two-dose vaccination of HepA. After full immunization, the seroconversion rates of anti-VZV antibodies were 91.79% in Group A and 92.15% in Group B; the geometric mean titers (GMTs) were 11.80 and 12.19, respectively. The seroconversion rates of anti-HAV antibodies were 99.48% in Group A and 100.0% in Group B; the geometric mean concentrations (GMCs) reached 9499.11 and 9528.36 mIU/ml, respectively. The lower limits of the 95% CI for the seroconversion difference of anti-VZV antibodies and anti-HAV antibodies were −5.86% and −2.90%, which greater than the predefined non-inferiority margin (−10%). The incidence rate of adverse reactions in Group A was lower than Group B (9.33% vs 16.22%), and only one serious adverse event was reported in Group B, which was unrelated to the study vaccine. In conclusion, the co-administration of VarV with HepA has non-inferior immunogenicity and safety profiles were quite comparable with the separate administration of both vaccines. Trial registration number: NCT05526820 (ClinicalTrials.gov).

Immunogenicity and Safety of a Booster Dose of Live Attenuated Varicella Vaccine, and Immune Persistence of a Primary Dose for Children Aged 2 to 6 Years.

Aim: To evaluate the immunogenicity and safety of a booster dose of live attenuated varicella vaccine (VarV) manufactured by Sinovac (Dalian) Vaccine Technology Co. Ltd., and the immune persistence of a primary dose in 2- to 6-year-old children. Methods: A phase IV, open-label study was conducted in China. Children previously vaccinated with a single dose of VarV at 1~3 years old received one dose of homologous VarV in the first year, the second year, or the third year after the primary immunization as booster immunization. Immune persistence was evaluated in an immune persistence analysis set, while immunogenicity was evaluated in a per-protocol analysis set, and safety was evaluated in a safety analysis set. The primary endpoint was the seropositive rate and the seroconversion rate of VarV antibody. The trial was registered at ClinicalTrials.gov (NCT02981836). Results: From July 2018 to August 2020, a total of 849 vaccinated children received the booster vaccination of VarV, one booster dose for each child (301 vaccinated in the first year after primary immunization (Group 1), 276 vaccinated in the second year after primary immunization (Group 2), 272 vaccinated in the third year after primary immunization (Group 3)). The seropositive rates were 99.34%, 97.83%, and 98.16% in Groups 1–3, with GMTs of 1:22.56, 1:18.49, and 1:18.45, respectively. Thirty days after the vaccine booster dose, the seropositive rates of the three groups were all 100% and the seroconversion rates were 52.54%, 67.46%, and 66.67%, with GMTs of 1:68.49, 1:76.32 and 1:78.34, respectively. The seroconversion rates in Groups 2 and 3 were both higher than that in Group 1 (p = 0.0005 and p = 0.0008). The overall incidence of adverse reactions was 7.77%, with 7.64%, 8.33%, and 7.35% in Groups 1, 2, and 3, respectively. The main symptom among adverse reactions was fever, the incidence of which ranged from 5.07% to 6.64% in each group, and no vaccine-related serious adverse events occurred. Conclusions: VarV had good immune persistence in 1~3 years after primary immunization. A vaccine booster dose for children aged 1~3 years after primary immunization recalled specific immune response to varicella-zoster virus, with no safety concerns increased.

Herpes Zoster in a 23-month-old Girl: A Case Report

&lt;p&gt;帶狀疱疹是潛伏在人體的水痘帶狀疱疹病毒再活化所造成。兒童帶狀疱疹狀並不常見，未滿兩歲更是罕見。本個案為1歲11個月大的女孩，過去未長過水痘，滿一歲時曾打過活性減毒的水痘疫苗。接種後第348天，在施打疫苗的左大腿（第三及第四腰椎的神經皮節）長出帶狀疱疹。經Acyclovir治療後，恢復迅速。依此個案的病史和臨床特徵推測，其帶狀疱疹可能是水痘疫苗所造成。若想確認帶狀疱疹在曾打過水痘疫苗的病人身上，到底是野生株或疫苗株的病毒所造成，最好的方法是做PCR檢驗。根據研究，水痘疫苗的確可能造成帶狀疱疹，但有施打疫苗者，其發生率和症狀均低於未施打疫苗者。整體而言，施打水痘疫苗，不僅能預防水痘，亦能預防帶狀疱疹，施打兩劑保護力更好。&lt;/p&gt; &lt;p&gt;&amp;nbsp;&lt;/p&gt;&lt;p&gt;Herpes zoster, caused by reactivation of the varicella-zoster virus (VZV), is not commonly seen in children, especially in those under 2 years of age. We reported a case of a 23-month-old girl with herpes zoster. She had no personal history of chicken pox. She was immunized with the live attenuated varicella vaccine at 12 months of age. Nevertheless, she developed herpes zoster in the left thigh (L3-L4 dermatomes) around the immunization site 348 days after the varicella vaccination. Her clinical symptoms improved rapidly after acyclovir treatment. Based on the personal history and clinical presentation, it is possible that her herpes zoster was caused by the virus of varicella vaccine. The best way to identify wild-type or vaccine-strain VZV in a herpes zoster patient with a prior history of varicella vaccination is by viral genome detection using polymerase chain reaction (PCR). As previous studies indicate, vaccine-strain herpes zoster can occur after varicella vaccine. However, the incidence and symptoms of herpes zoster occur less often in vaccinated individuals than in unvaccinated ones. In general, varicella vaccine can prevent not only varicella but also herpes zoster. The preventive effect of two-dose varicella vaccination is better than that of one-dose vaccination.&lt;/p&gt; &lt;p&gt;&amp;nbsp;&lt;/p&gt;

Live Attenuated Varicella Vaccine: Prevention of Varicella and of Zoster.

Michiaki Takahashi developed the live attenuated varicella vaccine in 1974 . This was the first, and is still the only, herpesvirus vaccine. Early studies showed promise, but the vaccine was rigorously tested on immunosuppressed patients because of their high risk of fatal varicella; vaccination proved to be lifesaving. Subsequently, the vaccine was found to be safe and effective in healthy children. Eventually, varicella vaccine became a component of measles mumps rubella vaccine, 2 doses of which are administered in the USA to ~90% of children. The incidence of varicella has dropped dramatically in the USA since vaccine-licensure in 1995. Varicella vaccine is also associated with a decreased incidence of zoster and is protective for susceptible adults. Today, immunocompromised individuals are protected against varicella due to vaccine-induced herd immunity. Latent infection with varicella zoster virus occurs after vaccination; however, the vaccine strain is impaired for its ability to reactivate.