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17 pages, 1502 KB  
Review
Perspectives on the History and Epidemiology of the Varicella Virus Vaccine and Future Challenges
by Masayuki Nagasawa
Pathogens 2025, 14(8), 813; https://doi.org/10.3390/pathogens14080813 - 16 Aug 2025
Viewed by 587
Abstract
The varicella attenuated virus vaccine, developed in Japan in the 1970s, has dramatically reduced the number of pediatric chickenpox cases over the past 30 years due to its widespread use. However, a small number of cases of chickenpox, shingles, aseptic meningitis, and acute [...] Read more.
The varicella attenuated virus vaccine, developed in Japan in the 1970s, has dramatically reduced the number of pediatric chickenpox cases over the past 30 years due to its widespread use. However, a small number of cases of chickenpox, shingles, aseptic meningitis, and acute retinal necrosis caused by vaccine strains have been reported. There are also issues that need to be addressed, such as breakthrough infections and the persistence of the preventive effect of vaccination. In addition, there is the possibility of the emergence of revertants or mutations in the vaccine strain. In recent years, subunit vaccines have been developed, their immune-stimulating effects have been demonstrated, and they are being applied clinically. In addition, development of an mRNA varicella vaccine is underway. In this review, the history and impact of the varicella vaccine are overviewed, as well as its future challenges. Full article
(This article belongs to the Special Issue Emerging and Re-Emerging Human Infectious Diseases)
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15 pages, 236 KB  
Article
Multifaceted Determinants of Varicella Vaccination Uptake Among Children Aged 1–10 Years in China: Findings of a Population-Based Survey Among 996 Parents
by Weijun Peng, Yuan Fang, Hongbiao Chen, Minjie Zhang, Yadi Lin and Zixin Wang
Vaccines 2025, 13(8), 810; https://doi.org/10.3390/vaccines13080810 - 30 Jul 2025
Viewed by 556
Abstract
Background/Objectives: Chickenpox is an ongoing health threat for young children. This study aimed to investigate varicella vaccination uptake among children and its determinants at both the individual and interpersonal levels. Methods: A cross-sectional survey of parents of children aged 0–15 years and with [...] Read more.
Background/Objectives: Chickenpox is an ongoing health threat for young children. This study aimed to investigate varicella vaccination uptake among children and its determinants at both the individual and interpersonal levels. Methods: A cross-sectional survey of parents of children aged 0–15 years and with administrative health records was conducted between September and October 2024 in Shenzhen, China. Participants were recruited through multistage random sampling. This analysis was based on a subsample of 996 parents whose children were 1–10 years old and without a prior history of chickenpox. Multivariate logistic regression models were fitted. Results: Among the participants, 47.0% reported that their children had received a varicella vaccination. Parents who believed that chickenpox was highly contagious (adjusted odds ratios [AOR]: 1.62, 95% confidence interval [CI]: 1.23, 2.13), perceived more benefits (AOR: 1.22, 95% CI: 1.05, 1.41) and cues to action (AOR: 1.33, 95% CI: 1.04, 1.69), and exhibited greater self-efficacy (AOR: 1.40, 95% CI: 1.09, 1.80) related to children’s varicella vaccination reported higher varicella vaccination uptake for their children. Greater perceived barriers related to vaccination (AOR: 0.89, 95% CI: 0.83, 0.95) and dysfunctional interactions with children (AOR: 0.97, 95% CI: 0.94, 0.99) were associated with lower varicella vaccination uptake for children. In addition, higher exposure to information encouraging parents to vaccinate their children against chickenpox (AOR: 1.24, 95%CI: 1.08, 1.41) and thoughtful consideration of the veracity of the information were associated with higher varicella vaccination uptake among children (AOR: 1.19, 95% CI: 1.05, 1.36). Conclusions: There is a strong need to promote varicella vaccination for children in China. Full article
(This article belongs to the Special Issue Acceptance and Hesitancy in Vaccine Uptake: 2nd Edition)
13 pages, 3525 KB  
Article
Epidemiologic Investigation of a Varicella Outbreak in an Elementary School in Gyeonggi Province, Republic of Korea
by Gipyo Sung, Jieun Jang and Kwan Lee
Children 2025, 12(7), 949; https://doi.org/10.3390/children12070949 - 18 Jul 2025
Viewed by 606
Abstract
Background/Objectives: On 6 June 2023, two varicella cases were reported at a highly vaccinated elementary school in Gyeonggi Province, Republic of Korea. We investigated the outbreak to describe its transmission dynamics; quantify attack rates in school, household, and private-academy settings; and assess [...] Read more.
Background/Objectives: On 6 June 2023, two varicella cases were reported at a highly vaccinated elementary school in Gyeonggi Province, Republic of Korea. We investigated the outbreak to describe its transmission dynamics; quantify attack rates in school, household, and private-academy settings; and assess the impact of coordinated control measures. Methods: A case-series study included 89 teachers and students who had contact with suspected patients. Using case definitions, laboratory tests, questionnaires, and environmental assessments, we evaluated exposures and factors facilitating spread. Results: Varicella developed in 23 of 89 contacts (25.8%); laboratory confirmation was obtained in 2 (8.7% of cases). The mean incubation period was 13 days. Epidemic-curve and network analyses indicated that the outbreak began with a single index case and extended through household contacts and private educational facilities, ultimately involving multiple schools. Conclusions: Breakthrough transmission can occur even when single-dose coverage exceeds 95%, particularly as vaccine-induced immunity may wane over time. Poorly regulated extracurricular facilities, such as private academies, act as bridging hubs that amplify spread across grades and even between schools. For timely detection and control, these venues should be incorporated into routine varicella surveillance, and rapid, coordinated infection-control measures are required across all educational settings. Full article
(This article belongs to the Special Issue Pediatric Infectious Disease Epidemiology)
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21 pages, 492 KB  
Review
Research Progress on Varicella-Zoster Virus Vaccines
by Hongjing Liu, Lingyan Cui, Sibo Zhang, Hong Wang, Wenhui Xue, Hai Li, Yuyun Zhang, Lin Chen, Ying Gu, Tingting Li, Ningshao Xia and Shaowei Li
Vaccines 2025, 13(7), 730; https://doi.org/10.3390/vaccines13070730 - 4 Jul 2025
Viewed by 1414
Abstract
Varicella-zoster virus (VZV) poses significant public health challenges as the etiological agent of varicella (chickenpox) and herpes zoster (HZ), given its high transmissibility and potential for severe complications. The introduction of VZV vaccines—particularly the vOka-based live attenuated and glycoprotein gE-based recombinant subunit vaccines—has [...] Read more.
Varicella-zoster virus (VZV) poses significant public health challenges as the etiological agent of varicella (chickenpox) and herpes zoster (HZ), given its high transmissibility and potential for severe complications. The introduction of VZV vaccines—particularly the vOka-based live attenuated and glycoprotein gE-based recombinant subunit vaccines—has substantially reduced the global incidence of these diseases. However, live attenuated vaccines raise concerns regarding safety and immunogenicity, especially in immunocompromised populations, while recombinant subunit vaccines, such as Shingrix, exhibit high efficacy but are associated with side effects and adjuvant limitations. Recent advancements in vaccine technology, including mRNA vaccines, viral vector vaccines, and virus-like particle (VLP) vaccines, offer promising alternatives with improved safety profiles and durable immunity. This review synthesizes current knowledge on VZV vaccine mechanisms, clinical applications, and immunization strategies, while also examining future directions in vaccine development. The findings underscore the pivotal role of VZV vaccines in disease prevention and highlight the need for continued research to enhance their public health impact. Full article
(This article belongs to the Special Issue Varicella and Zoster Vaccination)
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23 pages, 2678 KB  
Article
Validating the Predictions of a Dynamic Transmission Model Using Real-World Data from a Universal Varicella Vaccination Program in Germany
by Iwona Żerda, Tomasz Stanisz, Tomasz Fundament, Filip Chełmikowski, Wioletta Kłębczyk, Michał Pochopień, Emilie Clay, Samuel Aballéa and Mondher Toumi
J. Mark. Access Health Policy 2025, 13(2), 20; https://doi.org/10.3390/jmahp13020020 - 6 May 2025
Viewed by 534
Abstract
Dynamic transmission models (DTMs) have been used to estimate various aspects of the public health impact of varicella vaccination programs. The aim of this study was to validate the predictions of a DTM—developed using the typical approach to varicella modeling—using real-world data from [...] Read more.
Dynamic transmission models (DTMs) have been used to estimate various aspects of the public health impact of varicella vaccination programs. The aim of this study was to validate the predictions of a DTM—developed using the typical approach to varicella modeling—using real-world data from a country with a long-term universal varicella vaccination (UVV) program and to assess the sensitivity of the predictions to changes in model input parameters. A compartmental, age-stratified DTM was developed using the settings corresponding to the existing UVV program in Germany. The model-predicted total number of varicella cases followed the same trend as observed in the reported data. The agreement between the simulations’ results and the data was the highest for the age group most exposed to varicella (0–5 years old), while for other age groups, a decline in accuracy was observed. Sensitivity analyses identified the input parameters having a crucial impact on the model’s long-term predictions. The results supported the reliability of the DTM for assessing the impact of varicella vaccination programs over the first decades after their introduction and provided an insight into how certain parameters and assumptions influence the model output and thus require careful evaluation in the studies of future varicella vaccination programs. Full article
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19 pages, 341 KB  
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
Viewed by 2975
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)
9 pages, 1630 KB  
Case Report
Giant Cyst of Dermis-Fat Graft in a Child with MRSA—Case Report
by Biljana Kuzmanović Elabjer, Mirjana Bjeloš, Ana Ćurić, Daliborka Miletić and Mladen Bušić
Children 2025, 12(4), 457; https://doi.org/10.3390/children12040457 - 2 Apr 2025
Cited by 1 | Viewed by 613
Abstract
Background/Objectives: This case report presents a unique case of multiple postoperative complications, including sterile silicone implant extrusion, symblepharon formation, and the development of a giant cyst, following extensive multimodal chemotherapy for unilateral retinoblastoma in a pediatric patient. The case was further complicated by [...] Read more.
Background/Objectives: This case report presents a unique case of multiple postoperative complications, including sterile silicone implant extrusion, symblepharon formation, and the development of a giant cyst, following extensive multimodal chemotherapy for unilateral retinoblastoma in a pediatric patient. The case was further complicated by recurrent methicillin-resistant Staphylococcus aureus (MRSA) colonization, which persisted despite multiple eradication attempts. Methods: A 5-year-old boy presented with right-sided proptosis one year after receiving a secondary dermis-fat orbital graft. He had undergone 12 cycles of intravitreal, intra-arterial, and systemic chemotherapy as well as thermotherapy and cryotherapy due to recurrent retinoblastoma in the right eye. Following a third relapse, secondary enucleation was performed with a primary silicone orbital implant. However, extrusion of the implant occurred, and an orbital swab confirmed MRSA colonization. A secondary dermis-fat graft was harvested and implanted after ensuring MRSA clearance. A year later, the child developed rapid right-sided proptosis. Ultrasound revealed a cyst within the dermis-fat graft measured 23.6 mm in anteroposterior diameter. Surgery was postponed due to chickenpox, and the cyst enlarged reaching an anteroposterior diameter of 26.7 mm over two months. A complete excision was performed. Results: The surgery was uneventful. Intraoperative orbital swab was sterile, but MRSA was detected in a conjunctival swab, leading to treatment with local moxifloxacin drops and oral rifampicin. Conclusions: Giant cyst formation in a dermis-fat graft is an extremely rare complication. Complete excision remains the treatment of choice. However, in this case, it resulted in persistent anophthalmic socket syndrome, posing further reconstructive challenges. Full article
(This article belongs to the Special Issue Visual Deficits and Eye Care in Children)
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14 pages, 291 KB  
Review
Herpes Zoster: Risk Factors for Occurrence, Complications, and Recurrence with a Focus on Immunocompromised Patients
by Michał Oleszko, Paweł Zapolnik, Wojciech Kmiecik and Hanna Czajka
Diseases 2025, 13(3), 71; https://doi.org/10.3390/diseases13030071 - 26 Feb 2025
Cited by 1 | Viewed by 4350
Abstract
Background: The varicella-zoster virus is a highly contagious human herpesvirus that primarily causes varicella (chickenpox) as an initial infection, targeting T cells, neurons, as well as skin cells, and can later reactivate to cause herpes zoster (shingles). Following reactivation, the varicella-zoster virus infection [...] Read more.
Background: The varicella-zoster virus is a highly contagious human herpesvirus that primarily causes varicella (chickenpox) as an initial infection, targeting T cells, neurons, as well as skin cells, and can later reactivate to cause herpes zoster (shingles). Following reactivation, the varicella-zoster virus infection can lead to severe complications, the most common of which is postherpetic neuralgia. Risk factors include aging, immunosuppression, chronic diseases such as diabetes, cardiovascular disorders, respiratory conditions, and others. Objective: In this article, we present an analysis of factors increasing the risk of herpes zoster occurrence, complications, and recurrences (in particular in immunocompromised patients). Full article
(This article belongs to the Special Issue Infectious Disease Epidemiology 2024)
15 pages, 717 KB  
Review
Varicella Zoster Virus Infection and Pregnancy: An Optimal Management Approach
by Ana Ion, Olguța Anca Orzan and Beatrice Bălăceanu-Gurău
Pathogens 2025, 14(2), 151; https://doi.org/10.3390/pathogens14020151 - 5 Feb 2025
Cited by 2 | Viewed by 5919
Abstract
Varicella-zoster virus is an α-herpes virus with a double-stranded DNA genome, which causes two main clinical pictures: varicella or chickenpox and herpes zoster. Chickenpox is the primary infection, predominantly affecting children, and it presents with fever and a cutaneous eruption consisting of a [...] Read more.
Varicella-zoster virus is an α-herpes virus with a double-stranded DNA genome, which causes two main clinical pictures: varicella or chickenpox and herpes zoster. Chickenpox is the primary infection, predominantly affecting children, and it presents with fever and a cutaneous eruption consisting of a vesicular, pruritic, and painful rash. Herpes zoster is a viral infection that typically develops in adulthood as a result of the reactivation of the varicella-zoster virus. If acquired during pregnancy, chickenpox may be responsible for serious complications for the mother, the fetus, or the newborn. The most frequent complication of primary varicella-zoster virus infection in mothers is varicella pneumonia, while encephalitis and hepatitis are rare. The effects on the fetus due to chickenpox infection depend on the stage of pregnancy when the mother becomes infected. If the infection occurs during the first trimester, it does not increase the risk of miscarriage. However, if the infection occurs during the first or second trimester, it may cause fetal varicella syndrome or congenital varicella syndrome. During pregnancy, if the varicella-zoster virus reactivates, it usually does not cause harm to the fetus or lead to any birth defects. However, it may increase maternal morbidity due to herpes zoster and its complications. In the case of primary varicella-zoster virus infection in pregnant women, about 20% of newborns may get neonatal or infantile herpes zoster without any complications. However, it is recommended to start early treatment of herpes zoster in pregnant women as it is believed to accelerate the healing process of skin lesions and alleviate pain, reducing both its duration and severity. Through this narrative review, we discuss the approach to the optimal management of varicella-zoster virus infection during pregnancy. Full article
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20 pages, 1313 KB  
Article
DeepGenMon: A Novel Framework for Monkeypox Classification Integrating Lightweight Attention-Based Deep Learning and a Genetic Algorithm
by Abdulqader M. Almars
Diagnostics 2025, 15(2), 130; https://doi.org/10.3390/diagnostics15020130 - 8 Jan 2025
Cited by 4 | Viewed by 1429
Abstract
Background: The rapid global spread of the monkeypox virus has led to serious issues for public health professionals. According to related studies, monkeypox and other types of skin conditions can spread through direct contact with infected animals, humans, or contaminated items. This [...] Read more.
Background: The rapid global spread of the monkeypox virus has led to serious issues for public health professionals. According to related studies, monkeypox and other types of skin conditions can spread through direct contact with infected animals, humans, or contaminated items. This disease can cause fever, headaches, muscle aches, and enlarged lymph nodes, followed by a rash that develops into lesions. To facilitate the early detection of monkeypox, researchers have proposed several AI-based techniques for accurately classifying and identifying the condition. However, there is still room for improvement to accurately detect and classify monkeypox cases. Furthermore, the currently proposed pre-trained deep learning models can consume extensive resources to achieve accurate detection and classification of monkeypox. Hence, these models often need significant computational power and memory. Methods: This paper proposes a novel lightweight framework called DeepGenMonto accurately classify various types of skin diseases, such as chickenpox, melasma, monkeypox, and others. This suggested framework leverages an attention-based convolutional neural network (CNN) and a genetic algorithm (GA) to enhance detection accuracy while optimizing the hyperparameters of the proposed model. It first applies the attention mechanism to highlight and assign weights to specific regions of an image that are relevant to the model’s decision-making process. Next, the CNN is employed to process the visual input and extract hierarchical features for classifying the input data into multiple classes. Finally, the CNN’s hyperparameters are adjusted using a genetic algorithm to enhance the model’s robustness and classification accuracy. Compared to the state-of-the-art (SOTA) models, DeepGenMon features a lightweight design that requires significantly lower computational resources and is easier to train with few parameters. Its effective integration of a CNN and an attention mechanism with a GA further enhances its performance, making it particularly well suited for low-resource environments. DeepGenMon is evaluated on two public datasets. The first dataset comprises 847 images of diverse skin diseases, while the second dataset contains 659 images classified into several categories. Results: The proposed model demonstrates superior performance compared to SOTA models across key evaluation metrics. On dataset 1, it achieves a precision of 0.985, recall of 0.984, F-score of 0.985, and accuracy of 0.985. Similarly, on dataset 2, the model attains a precision of 0.981, recall of 0.982, F-score of 0.982, and accuracy of 0.982. Moreover, the findings demonstrate the model’s ability to achieve an inference time of 2.9764 s on dataset 1 and 2.1753 s on dataset 2. Conclusions: These results also show DeepGenMon’s effectiveness in accurately classifying different skin conditions, highlighting its potential as a reliable and low-resource tool in clinical settings. Full article
(This article belongs to the Section Machine Learning and Artificial Intelligence in Diagnostics)
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13 pages, 1045 KB  
Article
Has COVID-19 Affected the Course of Chickenpox in Children?
by Justyna Franczak, Zuzanna Wasielewska, Anna Maria Fotyga, Krystyna Dobrowolska, Justyna Moppert, Małgorzata Sobolewska-Pilarczyk and Małgorzata Pawłowska
Viruses 2024, 16(12), 1912; https://doi.org/10.3390/v16121912 - 13 Dec 2024
Viewed by 1544
Abstract
Objectives of the study: The aim of this study was to assess the impact of the COVID-19 pandemic on the epidemiology and clinical course of chickenpox in children based on 6 years of self-reported observations. MATERIAL AND METHODS: The medical records of 350 [...] Read more.
Objectives of the study: The aim of this study was to assess the impact of the COVID-19 pandemic on the epidemiology and clinical course of chickenpox in children based on 6 years of self-reported observations. MATERIAL AND METHODS: The medical records of 350 patients under 18 years of age hospitalised in the Department of Paediatrics, Infectious Diseases, and Hepatology between 1 January 2018 to 31 December 2023 were analysed retrospectively. RESULTS: During the analysed period, 350 children were hospitalised due to chickenpox, the fewest in the pandemic period, the greatest number in 2023. Complications of chickenpox were diagnosed in 297 children (84.86%). The most commonly diagnosed complications were bacterial dermatitis (168, 48%) and lower respiratory tract infections (13.42%). After the pandemic period, a generalised inflammatory reaction was observed significantly more often (p ≤ 0.01069). Among children hospitalised in 2023, 5.90% of patients with bacterial dermatitis required surgical intervention due to skin abscess or fasciitis. In 2023, 41.46% of cultures from swabs taken from skin lesions grew Streptococcus pyogenes. After the pandemic, children with chickenpox and gastrointestinal symptoms were hospitalised significantly less frequently (p ≤ 0.00001). CONCLUSIONS: In the post-pandemic period, there were more hospitalisations of patients with chickenpox complicated by bacterial skin infection progressing to a generalised inflammatory reaction or septicaemia, related to the increase in invasive group A streptococcal infections observed in Europe. On the other hand, thanks to the widespread adaption of hygiene practices and infection prevention measures, the number of patients with gastrointestinal symptoms significantly decreased. Full article
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18 pages, 2027 KB  
Article
TMS: Ensemble Deep Learning Model for Accurate Classification of Monkeypox Lesions Based on Transformer Models with SVM
by Elsaid Md. Abdelrahim, Hasan Hashim, El-Sayed Atlam, Radwa Ahmed Osman and Ibrahim Gad
Diagnostics 2024, 14(23), 2638; https://doi.org/10.3390/diagnostics14232638 - 23 Nov 2024
Cited by 7 | Viewed by 1871
Abstract
Background/Objectives:The emergence of monkeypox outside its endemic region in Africa has raised significant concerns within the public health community due to its rapid global dissemination. Early clinical differentiation of monkeypox from similar diseases, such as chickenpox and measles, presents a challenge. The Monkeypox [...] Read more.
Background/Objectives:The emergence of monkeypox outside its endemic region in Africa has raised significant concerns within the public health community due to its rapid global dissemination. Early clinical differentiation of monkeypox from similar diseases, such as chickenpox and measles, presents a challenge. The Monkeypox Skin Lesion Dataset (MSLD) used in this study comprises monkeypox skin lesions, which were collected primarily from publicly accessible sources. The dataset contains 770 original images captured from 162 unique patients. The MSLD includes four distinct class labels: monkeypox, measles, chickenpox, and normal. Methods: This paper presents an ensemble model for classifying the monkeypox dataset, which includes transformer models and support vector machine (SVM). The model development process begins with an evaluation of seven convolutional neural network (CNN) architectures. The proposed model is developed by selecting the top four models based on evaluation metrics for performance. The top four CNN architectures, namely EfficientNetB0, ResNet50, MobileNet, and Xception, are used for feature extraction. The high-dimensional feature vectors extracted from each network are then concatenated and optimized before being inputted into the SVM classifier. Results: The proposed ensemble model, in conjunction with the SVM classifier, achieves an accuracy of 95.45b%. Furthermore, the model demonstrates high precision (95.51%), recall (95.45%), and F1 score (95.46%), indicating its effectiveness in identifying monkeypox lesions. Conclusions: The results of the study show that the proposed hybrid framework achieves robust diagnostic performance in monkeypox detection, offering potential utility for enhanced disease monitoring and outbreak management. The model’s high diagnostic accuracy and computational efficiency indicate that it can be used as an additional tool for clinical decision support. Full article
(This article belongs to the Section Machine Learning and Artificial Intelligence in Diagnostics)
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18 pages, 4553 KB  
Article
Structures of the Varicella Zoster Virus Glycoprotein E and Epitope Mapping of Vaccine-Elicited Antibodies
by Wayne D. Harshbarger, Genevieve Holzapfel, Nishat Seraj, Sai Tian, Chelsy Chesterman, Zongming Fu, Yan Pan, Claire Harelson, Dongjun Peng, Ying Huang, Sumana Chandramouli, Enrico Malito, Matthew James Bottomley and James Williams
Vaccines 2024, 12(10), 1111; https://doi.org/10.3390/vaccines12101111 - 27 Sep 2024
Cited by 3 | Viewed by 3650
Abstract
Background: Varicella zoster virus (VZV) is the causative agent for chickenpox and herpes zoster (HZ, shingles). HZ is a debilitating disease affecting elderly and immunocompromised populations. Glycoprotein E (gE) is indispensable for viral replication and cell-to-cell spread and is the primary target for [...] Read more.
Background: Varicella zoster virus (VZV) is the causative agent for chickenpox and herpes zoster (HZ, shingles). HZ is a debilitating disease affecting elderly and immunocompromised populations. Glycoprotein E (gE) is indispensable for viral replication and cell-to-cell spread and is the primary target for anti-VZV antibodies. Importantly, gE is the sole antigen in Shingrix, a highly efficacious, AS01B-adjuvanted vaccine approved in multiple countries for the prevention of HZ, yet the three-dimensional (3D) structure of gE remains elusive. Objectives: We sought to determine the structure of VZV gE and to understand in detail its interactions with neutralizing antibodies. Methods: We used X-ray crystallography and cryo-electron microscopy to elucidate structures of gE bound by recombinant Fabs of antibodies previously elicited through vaccination with Zostavax, a live, attenuated vaccine. Results: The 3D structures resolve distinct central and C-terminal antigenic domains, presenting an array of diverse conformational epitopes. The central domain has two beta-sheets and two alpha helices, including an IgG-like fold. The C-terminal domain exhibits 3 beta-sheets and an Ig-like fold and high structural similarity to HSV1 gE. Conclusions: gE from VZV-infected cells elicits a human antibody response with a preference for the gI binding domain of gE. These results yield insights to VZV gE structure and immunogenicity, provide a framework for future studies, and may guide the design of additional herpesvirus vaccine antigens. Teaser: Structures of varicella zoster virus glycoprotein E reveal distinct antigenic domains and define epitopes for vaccine-elicited human antibodies. Full article
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11 pages, 599 KB  
Brief Report
Seroprevalence Assessment of Anti-Varicella Antibodies among Adults in the Province of Florence (Italy)
by Angela Bechini, Marco Del Riccio, Cristina Salvati, Benedetta Bonito, Beatrice Zanella, Massimiliano Alberto Biamonte, Mario Bruschi, Johanna Alexandra Iamarino, Letizia Fattorini, Lorenzo Baggiani, Monica Della Fonte, Giovanna Mereu, Paolo Bonanni, Working Group and Sara Boccalini
Vaccines 2024, 12(9), 1056; https://doi.org/10.3390/vaccines12091056 - 16 Sep 2024
Cited by 2 | Viewed by 1820
Abstract
Background: Varicella infections follow a benign course in around 90% of cases, with more severe forms occurring in adults. To identify potential pockets of susceptibility and to improve targeted immunization strategies, this study aims to critically assess immunological status by evaluating varicella seroprevalence [...] Read more.
Background: Varicella infections follow a benign course in around 90% of cases, with more severe forms occurring in adults. To identify potential pockets of susceptibility and to improve targeted immunization strategies, this study aims to critically assess immunological status by evaluating varicella seroprevalence among adults (18–99 years) in the province of Florence (Italy), nearly a decade after Tuscany introduced the vaccination program. Methods: A convenience sample of 430 subjects aged 18 to 94 years (mean age 51.8 ± 18.8 years), stratified by age and sex (53.7% of subjects were female; N = 231), was collected between 2018 and 2019. Sero-analytical analyses were conducted utilizing EUROIMMUN Anti-VZV ELISA (IgG) kits. Results: Most of them were of Italian nationality (87.4%; N = 376). Among the 430 tested samples, 385 (89.5%) were positive and 39 (9.1%) were negative. The remaining six sera (1.4%), confirmed as equivocal, were excluded from further analysis. No significant differences were found based on sex (p-value = 0.706) or nationality (p-value = 0.112). The application of trend tests (Mantel–Haenszel; Kendall Tau-b) showed a significant trend (p < 0.024 and p < 0.032, respectively), with an increasing probability of finding a positive anti-varicella serological status passing from a lower age group (84.2%) to a higher one (93.0%). By considering the female population aged 18–49 years, the seroprevalence of anti-varicella antibodies was found to be 88.4%, with a susceptibility of 11.6%, highlighting the risk of acquiring infection during pregnancy. Conclusions: The introduction of varicella vaccination has had a significant impact on public health in Tuscany and in Italy more generally. However, further efforts should be made to reduce the number of individuals still susceptible in adulthood, with particular attention given to women of childbearing age and the promotion of vaccination through mass and social media and institutional websites. Full article
(This article belongs to the Special Issue Research on Immune Response and Vaccines: 2nd Edition)
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15 pages, 2904 KB  
Article
Glycoprotein E-Displaying Nanoparticles Induce Robust Neutralizing Antibodies and T-Cell Response against Varicella Zoster Virus
by Hong Wang, Sibo Zhang, Wenhui Xue, Yarong Zeng, Liqin Liu, Lingyan Cui, Hongjing Liu, Yuyun Zhang, Lin Chen, Meifeng Nie, Rongwei Zhang, Zhenqin Chen, Congming Hong, Qingbing Zheng, Tong Cheng, Ying Gu, Tingting Li, Ningshao Xia and Shaowei Li
Int. J. Mol. Sci. 2024, 25(18), 9872; https://doi.org/10.3390/ijms25189872 - 12 Sep 2024
Cited by 5 | Viewed by 2380
Abstract
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 [...] Read more.
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. Full article
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