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Vaccines
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Varicella and Zoster Vaccination
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Varicella and Zoster Vaccination

A special issue of Vaccines (ISSN 2076-393X). This special issue belongs to the section "Vaccines against Tropical and other Infectious Diseases".

Deadline for manuscript submissions: 30 September 2025 | Viewed by 15659

Special Issue Editor

Dr. Peter Maple

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Guest Editor
1. Division of Clinical Neuroscience, Section of Clinical Neurology, University of Nottingham, Nottingham NG7 2UH, UK
2. Department of Neurology, Nottingham University Hospitals NHS Trust, Nottingham NG7 2UH, UK
Interests: human herpesviruses; neurodegenerative diseases; COVID-19
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Infection by the human herpesvirus known as varicella-zoster virus (VZV) is responsible for varicella. Varicella, commonly referred to as chickenpox, typically manifests as a rash in young immunocompetent children. This pursues a generally mild clinical course; rare complications include bacterial superinfection of skin lesions, pneumonia, and central nervous system manifestations. In adults, varicella can result in significant morbidity and even death. Varicella in immunocompromised individuals, maternal varicella, and congenital varicella are associated with significant risk of mortality. The host immunity established following VZV infection is usually lifelong; however, it does not result is clearance of the virus. VZV, much like other human herpesviruses, establishes latency, a condition in which the virus achieves a non-replicative state, effectively hiding it from the host’s immune response. In the case of VZV, latency is established in the sensory ganglia. In the event of the host’s immune response waning, the dormant VZV can assume a replicative (lytic) state, allowing zoster or shingles to occur.  Shingles is a debilitating disease, particularly in the event of post-herpetic neuralgia.

In temperate climates such as the UK, many children have experienced varicella by the age of 10 years and by adulthood in excess of 90% of the population has evidence of prior VZV infection. In tropical zones, VZV infection tends to occur in individuals of older age groups. Effective vaccines are available to prevent varicella; however, uptake has been variable following concerns that varicella vaccination may result in increased cases of zoster later in life. Recently, zoster vaccines have also become available. In this Special Issue, varicella and zoster epidemiology will be addressed together with the benefits of vaccination, both in relation to differing geographical regions and in the face of new infectious challenges (SARS-CoV-2) and associations with neurological diseases.

Dr. Peter Maple
Guest Editor

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Keywords

  • varicella-zoster virus
  • chickenpox
  • shingles
  • vaccination
  • epidemiology
  • geographical regions
  • neurological diseases
  • SARS-CoV-2

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Published Papers (9 papers)

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Research

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11 pages, 546 KiB  
Article
Post-Marketing Surveillance of Adverse Events for the Recombinant Zoster Vaccine Among the Population over 50 Years Old in Hangzhou, China
by Jing Wang, Jian Du, Yan Liu, Yuyang Xu, Jiayin Han and Xuechao Zhang
Vaccines 2024, 12(12), 1376; https://doi.org/10.3390/vaccines12121376 - 6 Dec 2024
Cited by 1 | Viewed by 891
Abstract
Objectives: This study aimed to evaluate the safety profile of the recombinant zoster vaccine (RZV) after its marketing in China. Methods: We present a descriptive analysis and safety signal assessment of adverse events following immunization (AEFI) associated with RZV between September 2020 and [...] Read more.
Objectives: This study aimed to evaluate the safety profile of the recombinant zoster vaccine (RZV) after its marketing in China. Methods: We present a descriptive analysis and safety signal assessment of adverse events following immunization (AEFI) associated with RZV between September 2020 and December 2023. The descriptive data collected includes demographic characteristics and the classification of characteristics of AEFI cases, while vaccine safety signal assessment was evaluated using the reporting odds ratio (ROR). Results: In total, we documented 275 AEFI cases following RZV vaccination, with a reporting rate of 76.22/10,000 doses administered. Notably, only one case was classified as serious, and the reporting rates were significantly higher among females, individuals aged 50–59 years, and those residing in rural areas. Furthermore, the reporting rate for the first dose exceeded that for the second dose. Among the reported AEFI cases, 98.91% were attributed to vaccine product-related reactions, and 97.45% were initially reported by either the vaccine recipient or their guardians. The interval between vaccination and symptom onset was predominant within 3 d after vaccination. The disproportionality analysis identified five positive signals—fever (37.5–38.5 °C), injection site reactions greater than 5 cm, pain, Henoch Schönlein purpura (HSP), and swelling—which suggests a stronger association with the RZV than the expected threshold. Conclusion: In summary, RZV demonstrated a favorable safety profile. However, continued monitoring and research on the long-term safety implications of RZV are needed. Full article
(This article belongs to the Special Issue Varicella and Zoster Vaccination)
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12 pages, 1501 KiB  
Article
Comparison of ELISA Versus FAMA Titers in Children After Chemotherapy and Hematopoietic Stem Cell Transplantation Who Received the Live Attenuated MAV/06 Strain Varicella Vaccine
by Bin Ahn, Kyu Ri Kang, Ye Ji Kim, Yoon Kyung Cho, Suejung Jo, Jae won Yoo, Jae Wook Lee, Nack-Gyun Chung, Bin Cho, Dae Chul Jeong, Jin Han Kang and Hyun Mi Kang
Vaccines 2024, 12(12), 1371; https://doi.org/10.3390/vaccines12121371 - 5 Dec 2024
Viewed by 921
Abstract
Background: Varicella can lead to severe complications in immunocompromised children, including those undergoing hematopoietic stem cell transplantation (HSCT) or chemotherapy. Preventing primary varicella zoster virus (VZV) infection is crucial in these populations to mitigate morbidity and mortality. This study aimed to evaluate the [...] Read more.
Background: Varicella can lead to severe complications in immunocompromised children, including those undergoing hematopoietic stem cell transplantation (HSCT) or chemotherapy. Preventing primary varicella zoster virus (VZV) infection is crucial in these populations to mitigate morbidity and mortality. This study aimed to evaluate the immunogenicity and safety of the live attenuated MAV/06 varicella vaccine in pediatric patients post-HSCT and post-chemotherapy. Additionally, it sought to compare fluorescent-antibody-to-membrane-antigen (FAMA) and enzyme-linked immunosorbent assay (ELISA) titers to establish effective cut-off levels for protection against varicella. Methods: The FAMA assay was conducted at the Vaccine Bio Research Institute, and a VARICELLA-ZOSTER ELISA (Vircell, Granada, Spain) kit, which relies on lysate from whole cells infected with VZV, was used to determine VZV IgG. A prospective cohort study was conducted with 76 pediatric patients under 18 years old who tested negative for VZV IgG via ELISA. Patients post-HSCT and post-chemotherapy were included. Participants received the MAV/06 varicella vaccine, and serologic responses were evaluated using ELISA and FAMA. Results: The median age of participants was 9.8 years, with acute lymphoid leukemia and acute myeloid leukemia being the most common underlying disease. Post-dose 1, the seropositive rate was 56.1% by ELISA and 97.2% by FAMA. Based on the FAMA seropositive cut-off ≥1:4, post-dose 1 geometric mean titers (GMTs) of seropositive patients in the post-HSCT group were 14.7 (95% CI, 11.3–19.1) versus 20.2 (95% CI, 13.0–31.3) in the post-chemotherapy group (p = 0.690). Based on a FAMA seropositive cut-off ≥1:16, the post-dose 1 GMT of patients considered seropositive in the post-HSCT group was 19.3 (95% CI, 15.6–24.0) versus 34.1 (95% CI, 21.0–55.4) in the post-chemotherapy group (p = 0.116), and post-dose 2 FAMA titers of 76.1 (95% CI, 14.6–398.1) in the post-HSCT group and 64.0 (95% CI, 11.4–358.1) in the post-HSCT group (p = 0.853) were observed. In patients with lower baseline FAMA titers (1:4 to 1:8), 66.7% in the post-HSCT group and 71.5% in the post-chemotherapy group achieved a greater than four-fold increase in FAMA titers post-dose 1, while those with higher baseline titers (≥1:16) did not. There were no serious adverse events or vaccine-related rashes occurring in any of the patients. Conclusion: The MAV/06 varicella vaccine is immunogenic in pediatric patients post-HSCT and post-chemotherapy, particularly when administered in a two-dose schedule using a cut-off FAMA titer of <1:16. Full article
(This article belongs to the Special Issue Varicella and Zoster Vaccination)
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16 pages, 1006 KiB  
Article
Varicella-Zoster Disease of the Central Nervous System in Immunocompetent Children: Case Series and a Scoping Review
by Dawid Lewandowski, Kacper Toczylowski, Malgorzata Kowalska, Milena Krasnodębska, Iryna Krupienko, Karolina Nartowicz, Magdalena Sulik and Artur Sulik
Vaccines 2024, 12(9), 1086; https://doi.org/10.3390/vaccines12091086 - 23 Sep 2024
Cited by 2 | Viewed by 1645
Abstract
Background: Varicella-Zoster Virus (VZV) is characterized by its ability to enter a dormant state within the body. When the wild or vaccine virus reactivates, it can lead to herpes zoster (HZ), which infrequently manifests as a neuroinfection. Objectives: The aim of the study [...] Read more.
Background: Varicella-Zoster Virus (VZV) is characterized by its ability to enter a dormant state within the body. When the wild or vaccine virus reactivates, it can lead to herpes zoster (HZ), which infrequently manifests as a neuroinfection. Objectives: The aim of the study was to analyze the clinical manifestations and outcomes associated with VZV reactivation in the CNS in immunocompetent children. Methods: We searched medical databases for case reports using the keywords “zoster”, “meningitis”, “encephalitis”, and “immunocompetent”. The inclusion criteria were age below 18 years, any gender, race, and ethnicity, no features or history of immunodeficiency, and confirmation of VZV reactivation through the detection of VZV DNA in the CSF. Patients were categorized into two groups: children experiencing the reactivation of the wild virus and children with the vaccine strain virus. Results: The cohort included six children hospitalized in our hospital and 49 children reported in the literature. In 37 (67%), a wild-type virus was detected, while in 18 (33%), an infection was caused by the vaccine strain. There were no differences in the clinical presentation between the two groups. A typical rash was observed in 32 (58%) children. Approximately 41 of the 55 children (75%) received antiviral treatment. Four patients experienced complications. Conclusions: Neither a history of VZV immunization nor the absence of a skin rash can definitively exclude VZV meningitis. It is important to note that any seemingly healthy child, regardless of recognized risk factors, could develop HZ meningitis. Full article
(This article belongs to the Special Issue Varicella and Zoster Vaccination)
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11 pages, 517 KiB  
Article
The Influence of Altitude, Urbanization, and Local Vaccination Centers on Vaccine Uptake within an Italian Health District: An Analysis of 15,000 Individuals Eligible for Vaccination
by Andrea Ceccarelli, Giorgia Soro, Chiara Reali, Emilia Biguzzi, Roberta Farneti, Valeria Frassineti, Raffaella Angelini, Gian Luigi Belloli, Davide Gori and Marco Montalti
Vaccines 2024, 12(8), 875; https://doi.org/10.3390/vaccines12080875 - 2 Aug 2024
Cited by 1 | Viewed by 1141
Abstract
In Italy, free vaccinations for Herpes Zoster (HZ), pneumococcal (PCV), and influenza (FLU) are recommended each year for individuals turning 65. Despite this, achieving optimal vaccination coverage remains challenging. This study assesses coverage rates for HZ, PCV, and FLU in Forlì, Northern Italy, [...] Read more.
In Italy, free vaccinations for Herpes Zoster (HZ), pneumococcal (PCV), and influenza (FLU) are recommended each year for individuals turning 65. Despite this, achieving optimal vaccination coverage remains challenging. This study assesses coverage rates for HZ, PCV, and FLU in Forlì, Northern Italy, and examines how altitude, urban planning, and health organization variables (such as the presence of a vaccination center) impact vaccine uptake. Vaccination coverages were calculated for birth cohorts between 1952 and 1958 for each municipality in the Forlì area as of 1 March 2024. The geographical factors influencing the vaccination uptake were extracted from the Italian National Institute of Statistics (ISTAT) records and evaluated through a multivariate analysis. The sample analyzed included 15,272 vaccine campaign targets from Forlì’s province (185,525 citizens); the vaccine uptake rates for HZ, PCV, and FLU were 26.9%, 36.7%, and 43.5%, respectively. Gender did not appear to influence vaccine uptake. Living in a flat area appeared to increase vaccine uptake in a statistically significant way for all the vaccinations when compared to a mountainous area (HZ: OR: 1.50, PCV: OR: 1.33, FLU: OR: 1.67). The presence of a vaccine service in low-urbanized areas was shown to increase vaccine uptake for all vaccinations (HZ: OR: 1.65, PCV: OR: 1.93, FLU: OR: 1.53) compared with low-urbanized areas without a vaccination center or more urbanized areas with a vaccination center. This study emphasizes the significance of the territorial context, along with the ease of access to vaccinations and geographic barriers, as key determinants in achieving vaccination targets. Local health authorities should consider these factors when implementing vaccination campaigns. Full article
(This article belongs to the Special Issue Varicella and Zoster Vaccination)
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12 pages, 559 KiB  
Article
The Burden of Herpes Zoster on Hospital Admissions: A Retrospective Analysis in the Years of 2015–2021 from the Abruzzo Region, Italy
by Piera Scampoli, Giuseppe Di Martino, Fabrizio Cedrone, Camillo Odio, Pamela Di Giovanni, Ferdinando Romano and Tommaso Staniscia
Vaccines 2024, 12(5), 462; https://doi.org/10.3390/vaccines12050462 - 26 Apr 2024
Cited by 5 | Viewed by 1609
Abstract
(1) Background: Herpes zoster (HZ) is a disease caused by the reactivation of the Varicella Zoster Virus (VZV). Clinical reactivation, herpes zoster, takes place in 10–20% of subjects who contracted the primary infection, with a higher risk of developing zoster increasing proportionally with [...] Read more.
(1) Background: Herpes zoster (HZ) is a disease caused by the reactivation of the Varicella Zoster Virus (VZV). Clinical reactivation, herpes zoster, takes place in 10–20% of subjects who contracted the primary infection, with a higher risk of developing zoster increasing proportionally with age, especially after 50 years of age. HZ is a common clinical problem, particularly among patients aged over 50 years and immunocompromised patients. Immunocompromised patients and adults could present an atypical and more severe course. In addition, they are at greater risk of complications. For this reason, it is important to understand the real burden of the disease and to identify the subjects who are at higher risk of HZ and its complications, also to direct preventive strategies at the right targets. The aim of the present study is to analyze HZ-related hospitalization trends in Abruzzo in the period of 2015–2021. (2) Methods: Data related to hospital admissions were extracted from the hospital discharge records (HDRs) of the whole region, considering all admissions during the years of 2015–2021. The trends in hospital admissions and length of stay were evaluated and analyzed. (3) Results: A total of 768 hospital discharges with a diagnosis of herpes zoster were registered in Abruzzo during the 7-year study period. During the study period, an increasing trend was observed from the year 2015 to the year 2017, ranging from 8.19 cases/100,000 to 11.5 cases/100,000 (APC (Annual percentage change) +20.8%; 95%CI −2.3; 47.6). After the year 2017, a significantly decreasing trend was observed, reaching 5.46 cases/100,000 in the year 2021 (APC −18.4%; 95%CI −31.5; −12.0). Across the entire study period, an average annual percentage change (AAPC) of −7.0% (95%CI −13.0; −1.3) was observed. (4) Conclusions: Despite the trend of a reduction in hospitalizations, this study highlights that HZ continues to have a great impact on public health. So, it is important to update recommendations for the use of the already available HZ vaccine and to implement new strategies to increase awareness of the prevention of the disease. Full article
(This article belongs to the Special Issue Varicella and Zoster Vaccination)
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13 pages, 1463 KiB  
Article
Study on Varicella-Zoster Virus Antibody Levels among Children Aged 1–7 Years in Changzhou, China
by Dan Wu, Changlei Han, Suting Xiong, Peipei Zhang, Han Gao, Junhong Li, Fengming Wang, Qinwen Xu and Xin Dong
Vaccines 2024, 12(3), 290; https://doi.org/10.3390/vaccines12030290 - 11 Mar 2024
Cited by 2 | Viewed by 3011
Abstract
We aim to understand the varicella-zoster virus (VZV) antibody levels in children after vaccination and to construct VZV-IgG centile curves and reference values for children aged 1–7 years. From September to October 2023, a total of 806 children were recruited according to the [...] Read more.
We aim to understand the varicella-zoster virus (VZV) antibody levels in children after vaccination and to construct VZV-IgG centile curves and reference values for children aged 1–7 years. From September to October 2023, a total of 806 children were recruited according to the time intervals of 1 month, 6 months, 1 year, 2 years, and 3 years after vaccination, as well as age groups. A generalized additive model for location, shape, and scale (GAMLSS) was applied to estimate P3, P10, P25, P50, P75, P90, and P97 centile reference values of VZV-IgG, and 95% reference intervals were calculated. A total of 785 children were included in the analysis, with an overall positivity rate of 70.3%, a median antibody concentration of 192.05 (82.89–571.14) mIU/mL, and a positivity rate of 57.7% for one dose of vaccine and 84.2% for two doses. Antibody positivity rates at 1 month, 6 months, 1 year, 2 years, and 3 years after vaccination were 65.1%, 74.4%, 80.4%, 67.7%, and 63.0%, respectively. The GAMLSS results showed that VZV-IgG had a tendency to increase and then decrease after vaccination, and the second dose of vaccination could significantly increase VZV-IgG. Two doses of varicella vaccine should be administered to children in a timely manner and included in the routine vaccination programs. Full article
(This article belongs to the Special Issue Varicella and Zoster Vaccination)
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Review

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19 pages, 341 KiB  
Review
Herpes Zoster Vaccination: Insights into Efficacy, Safety, and Guidelines
by Michał Oleszko, Paweł Zapolnik and Hanna Czajka
Vaccines 2025, 13(5), 477; https://doi.org/10.3390/vaccines13050477 - 28 Apr 2025
Abstract
Background: The varicella–zoster virus (VZV) is a human herpesvirus that primarily causes varicella (chickenpox) as an initial infection, characterized by distinctive skin lesions. It can later reactivate, leading to herpes zoster (shingles). Once reactivated, VZV infection may result in serious complications, the most [...] Read more.
Background: The varicella–zoster virus (VZV) is a human herpesvirus that primarily causes varicella (chickenpox) as an initial infection, characterized by distinctive skin lesions. It can later reactivate, leading to herpes zoster (shingles). Once reactivated, VZV infection may result in serious complications, the most common being postherpetic neuralgia. Fortunately, vaccination can prevent this condition. Objectives: In this study, we provide a comprehensive analysis of zoster vaccines, including clinical trials, safety profiles, and reimbursement guidelines across various countries. Results: Our findings confirm the vaccine’s effectiveness and safety across diverse populations, aligning with previous clinical trials and real-world data, and summarize global vaccination guidelines. Full article
(This article belongs to the Special Issue Varicella and Zoster Vaccination)
51 pages, 17087 KiB  
Review
Immunity to Varicella Zoster Virus in Healthcare Workers: A Systematic Review and Meta-Analysis (2024)
by Matteo Riccò, Pietro Ferraro, Salvatore Zaffina, Vincenzo Camisa, Federico Marchesi, Francesca Fortin Franzoso, Cosimo Ligori, Daniel Fiacchini, Nicola Magnavita and Silvio Tafuri
Vaccines 2024, 12(9), 1021; https://doi.org/10.3390/vaccines12091021 - 6 Sep 2024
Cited by 2 | Viewed by 3371
Abstract
Healthcare workers (HCWs) are occupationally exposed to varicella zoster virus (VZV), and their inappropriate vaccination status could contribute to an outbreak involving both professionals and the patients they care for, with a potential impact on the general population. Therefore, since 2007, the Advisory [...] Read more.
Healthcare workers (HCWs) are occupationally exposed to varicella zoster virus (VZV), and their inappropriate vaccination status could contribute to an outbreak involving both professionals and the patients they care for, with a potential impact on the general population. Therefore, since 2007, the Advisory Committee on Immunization Practices (ACIP) recommends that all HCWs have evidence of immunity against varicella. The present meta-analysis was therefore designed to collect the available evidence on the seronegative status of VZV among HCWs. PubMed, Scopus, and Embase databases were searched without backward limit for articles reporting on the seroprevalence of VZV among HCWs, and all articles meeting the inclusion criteria were included in a random-effect meta-analysis model. From 1744 initial entries, a total of 58 articles were included in the quantitative analysis (publication range: 1988 to 2024), for a pooled sample of 71,720 HCWs. Moreover, the included studies reported on seroprevalence data on measles (N = 36,043 HCWs) and rubella (N = 22,086 HCWs). Eventually, the pooled seronegative status for VZV was estimated to be 5.72% (95% confidence interval [95% CI] 4.59 to 7.10) compared to 6.91% (95% CI 4.79 to 9.87) for measles and 7.21% (5.36 to 9.64) for rubella, with a greater risk among subjects younger than 30 years at the time of the survey (risk ratio [RR] 1.434, 95% CI 1.172 to 1.756). Interestingly, medical history of either VZV infection/vaccination had low diagnostic performances (sensitivity 76.00%; specificity 60.12%; PPV of 96.12% but PNV of 18.64%). In summary, the available data suggest that newly hired HCWs are increasingly affected by low immunization rates for VZV but also for measles and rubella, stressing the importance of systematically testing test newly hired workers for all components of the measles–pertussis–rubella–varicella vaccine. Full article
(This article belongs to the Special Issue Varicella and Zoster Vaccination)
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Other

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26 pages, 3068 KiB  
Systematic Review
Immunogenicity of Recombinant Zoster Vaccine: A Systematic Review, Meta-Analysis, and Meta-Regression
by Lorenzo Losa, Ippazio Cosimo Antonazzo, Giuseppe Di Martino, Giampiero Mazzaglia, Silvio Tafuri, Lorenzo Giovanni Mantovani and Pietro Ferrara
Vaccines 2024, 12(5), 527; https://doi.org/10.3390/vaccines12050527 - 11 May 2024
Cited by 4 | Viewed by 2283
Abstract
Background: The adjuvanted recombinant zoster vaccine (RZV), consisting of varicella-zoster virus glycoprotein E (gE) and the AS01B adjuvant system, effectively prevents herpes zoster (HZ). In the absence of a well-defined correlate of protection, it is important to monitor the RZV immune response, [...] Read more.
Background: The adjuvanted recombinant zoster vaccine (RZV), consisting of varicella-zoster virus glycoprotein E (gE) and the AS01B adjuvant system, effectively prevents herpes zoster (HZ). In the absence of a well-defined correlate of protection, it is important to monitor the RZV immune response, as a proxy of clinical effectiveness. Methods: This systematic review examined post-vaccination parameters: humoral and cell-mediated immunity, avidity index, geometric mean concentration of antibody (GMC), and immunity persistence. The meta-analysis used a random-effects model, and subgroup and meta-regression analyses were conducted. Results: Among 37 included articles, after one month from RZV-dose 2, the pooled response rate for anti-gE humoral immunity was 95.2% (95%CI 91.9–97.2), dropping to 77.6% (95%CI 64.7–86.8) during immunosuppression. The anti-gE cell-mediated immunity-specific response reached 84.6% (95%CI 75.2–90.9). Varying factors, such as age, sex, coadministration with other vaccines, prior HZ, or live-attenuated zoster vaccine, did not significantly affect response rates. RZV induced a substantial increase in gE avidity. Immunity persistence was confirmed, with more rapid waning in the very elderly. Conclusions: This systematic review indicates that RZV elicits robust immunogenicity and overcomes immunocompromising conditions. The findings underscore the need for further research, particularly on long-term immunity, and have the potential to support HZ vaccination policies and programs. Full article
(This article belongs to the Special Issue Varicella and Zoster Vaccination)
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