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13 pages, 732 KB  
Review
Vaccination Against Herpes Zoster in Adults: Current Strategies in European Union Countries
by Manuela Chiavarini, Angela Bechini, Sara Boccalini, Alisa Barash, Enrica Castellana, Alessandro Senape and Paolo Bonanni
Vaccines 2025, 13(10), 1073; https://doi.org/10.3390/vaccines13101073 - 20 Oct 2025
Viewed by 316
Abstract
Background/Objectives: Herpes zoster (HZ), caused by varicella zoster virus (VZV) reactivation, significantly affects the functional status and quality of life of older adults and immunocompromised individuals. Vaccination represents an effective strategy to reduce the incidence of HZ. Methods: This review offers a cross-sectional [...] Read more.
Background/Objectives: Herpes zoster (HZ), caused by varicella zoster virus (VZV) reactivation, significantly affects the functional status and quality of life of older adults and immunocompromised individuals. Vaccination represents an effective strategy to reduce the incidence of HZ. Methods: This review offers a cross-sectional assessment of the current landscape of adult herpes zoster vaccination strategies across the 27 EU member states, drawing on data available up to July 2025 from official sources such as the ECDC, the WHO, and national health authorities. Results: HZ vaccination is recommended in 17 EU countries (63%) according to the National Immunization Programs (NIPs) or by other institutional national health documents; in only 7 countries, vaccination is fully covered by the national healthcare system. HZ vaccination is recommended for healthy adults aged ≥50 years in 23.5% of countries (4/17), ≥60 years in 29.4% (5/17), and ≥65 years in 41.2% (7/17). At-risk groups are targeted in 94.1% of countries (16/17), predominantly from age 18 years (14 countries). Conclusions: An overall tendency toward broader HZ vaccination strategies, targeting both older adults and risk groups, is emerging. However, differences among national policies, together with the European Commission’s withdrawal of the live-attenuated Zostavax vaccine effective 1 June 2025, highlight the urgent need for comprehensive, harmonized immunization strategies to ensure adequate coverage of adult HZ vaccination across Europe. Full article
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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 5 | Viewed by 4277
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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15 pages, 2469 KB  
Article
Immunogenicity in Mice Immunized with Recombinant Adenoviruses Expressing Varicella-Zoster Virus Envelope Glycoprotein E
by Yanpeng Zheng, Lei Huang, Huiru Ding, Huawei Xu, Rigan Shu, Jiemei Yu, Xianglei Peng, Yuanhui Fu and Jinsheng He
Viruses 2023, 15(12), 2288; https://doi.org/10.3390/v15122288 - 22 Nov 2023
Cited by 2 | Viewed by 2271
Abstract
Herpes zoster (HZ) is a disease caused by the reactivation of latent varicella-zoster virus (VZV). The subunit vaccine, Shingrix®, and live attenuated vaccine, Zostavax®, could be used as an HZ vaccine that prevents HZ from being developed due to [...] Read more.
Herpes zoster (HZ) is a disease caused by the reactivation of latent varicella-zoster virus (VZV). The subunit vaccine, Shingrix®, and live attenuated vaccine, Zostavax®, could be used as an HZ vaccine that prevents HZ from being developed due to the reactivation of latent VZV in the sensory ganglia due to aging, stress or immunosuppression. In this study, the recombinant adenoviruses rChAd63/gE expressing glycoprotein E (gE) of VZV based on chimpanzee adenovirus serotype 63 (ChAd63) were constructed and investigated for the immunogenicity of different immune pathways in C57BL/6 mice. The results showed similar CD4+ T and CD8+ T cell responses to Shingrix® were induced in mice vaccinated using rChAd63/gE via different immune pathways. This study elucidates that recombinant adenoviruses expressing VZV gE could be appropriate for further development as a new HZ vaccine candidate via different immune pathways. Full article
(This article belongs to the Section Viral Immunology, Vaccines, and Antivirals)
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9 pages, 520 KB  
Communication
Surveying a Sample of the Spanish Ophthalmologic Community about Vaccination against Herpes Zoster
by Alberto Sánchez-Mellado, Luis Alcaraz-Clemente, Marina Rodríguez-Calvo-de-Mora, José-María Sánchez-González, Santiago Ortiz-Perez and Carlos Rocha-de-Lossada
Vaccines 2023, 11(5), 952; https://doi.org/10.3390/vaccines11050952 - 5 May 2023
Cited by 2 | Viewed by 2160
Abstract
There are currently two authorized vaccines against herpes zoster (HZ) that have been shown to be safe and effective in its prevention: Zostavax, a zoster vaccine live (ZVL), and Shingrix, a recombinant zoster Vaccine (RZV). Because ophthalmologists work with vision-threatening complications of zoster, [...] Read more.
There are currently two authorized vaccines against herpes zoster (HZ) that have been shown to be safe and effective in its prevention: Zostavax, a zoster vaccine live (ZVL), and Shingrix, a recombinant zoster Vaccine (RZV). Because ophthalmologists work with vision-threatening complications of zoster, such as herpes zoster ophthalmicus (HZO), they are in a good position to advocate for vaccination. Our aim was to determine the current knowledge among Spanish ophthalmologists about the effectiveness of the available vaccines against HZ. A Google Forms questionnaire was created and used as the survey platform for this study. It was an anonymous online survey of 16 questions, which was shared among Spanish ophthalmologists in-training and consultants from 27 April 2022 to 25 May 2022. The survey was completed by a total of 206 ophthalmologists of all subspecialties. We obtained responses from 17 of the 19 regions of Spain. Fifty-five percent of the respondents agreed that HZ is a frequent cause of vision loss. However, 27% of the professionals were unaware of the existence of vaccines against HZ and 71% of them did not know in which cases it could be indicated. Only nine ophthalmologists (4%) had ever suggested vaccination against HZ to their patients. Despite this, 93% considered it important to recommend vaccination against HZ if it proved to be safe and effective. Considering the sequelae, complications, and the existence of safe and effective vaccines against HZ, vaccination of the target population could be considered an important public health measure. We are convinced that it is time for ophthalmologists to take an active role in HZO prevention. Full article
(This article belongs to the Section Vaccines and Public Health)
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8 pages, 245 KB  
Article
Adherence to Herpes Zoster (Shingles) Catch-Up Campaign at the Romagna Local Health Authority (Italy), a Multi-Center Retrospective Observational Study
by Andrea Ceccarelli, Susan Scrimaglia, Virginia Fossi, Luigi Ceccaroni, Andrea Federici, Chiara Reali, Raffaella Angelini, Giulia Silvestrini, Francesco Sintoni, Maria Pia Fantini, Davide Gori, Francesca Righi and Marco Montalti
Vaccines 2022, 10(10), 1770; https://doi.org/10.3390/vaccines10101770 - 21 Oct 2022
Cited by 6 | Viewed by 2995
Abstract
Herpes Zoster (shingles) is an infection that occurs when varicella-zoster virus reactivates from the latent state. Incidence and severity of Herpes Zoster disease increase with age. Antiviral drugs are the elective treatment; however, prevention of disease reactivation through effective and safe vaccines is [...] Read more.
Herpes Zoster (shingles) is an infection that occurs when varicella-zoster virus reactivates from the latent state. Incidence and severity of Herpes Zoster disease increase with age. Antiviral drugs are the elective treatment; however, prevention of disease reactivation through effective and safe vaccines is available in Italy out-of-pocket from age 65 onwards. The Romagna Local Health Authority (northern Italy) administered catch-up vaccinations in March–May 2022 for immunizations not performed during the COVID-19 pandemic. In this study, adherence rates to the catch-up campaign and recall activities adopted in two centers were investigated. The uptakes for only the catch-up vaccinations were 11.4% and 12.4%. Having suffered from Herpes Zoster or having family members who suffered from it would not seem to be drivers of increased uptake. Although sending text-messages to all involved patients was the main motivation for vaccine uptake (85.7–95.1%), word of mouth and web/news advertising also contributed to adoption in Center No. 2. In both centers, the need for greater synergy between public health departments and general practitioners to engage their patients emerged, as did the need for additional recall measures. Studying the main drivers of vaccine hesitancy, especially at the local level, can help in targeting campaigns and catch-up activities in order to achieve widespread acceptance. Full article
(This article belongs to the Special Issue Feature Papers of Epidemiology and Vaccines 2.0)
14 pages, 2237 KB  
Article
Ageing of Immune System and Response to a Live-Attenuated Herpes Zoster Vaccine in Lung Transplant Candidates
by Lei Wang, Erik A.M. Verschuuren, Davy Paap, Christien Rondaan, Elisabeth Raveling-Eelsing, Siqi Liu, Johanna Westra and Nicolaas A. Bos
Vaccines 2021, 9(3), 202; https://doi.org/10.3390/vaccines9030202 - 28 Feb 2021
Cited by 10 | Viewed by 3038
Abstract
The mean age of lung transplant recipients has significantly increased in recent decades. Elderly recipients have a higher risk of developing herpes zoster (HZ), and they have in general a worse response to vaccination than younger persons do. We investigated the relationship between [...] Read more.
The mean age of lung transplant recipients has significantly increased in recent decades. Elderly recipients have a higher risk of developing herpes zoster (HZ), and they have in general a worse response to vaccination than younger persons do. We investigated the relationship between the humoral and cellular immune response to a live-attenuated HZ vaccine (Zostavax®, Merck Sharp and Dohme) and the frequencies of T and B cell subsets, especially aged cell subsets (CD28−T cells and age associated B cells, ABCs). In total, 37 patients awaiting lung transplantation received one dose of Zostavax®, and peripheral blood was collected before and within 6 months after vaccination. We observed a robust immune response after vaccination. The frequencies of CD28−T cells before vaccination had no impact on the subsequent immune response to HZ vaccination. However, a higher frequency of ABCs before vaccination correlated with a lower immune response especially regarding the cellular immune response. Cytomegalovirus seropositivity was associated with increased frequencies of CD28−T cells but not with frequencies of ABCs in the patients. In conclusion, increased levels of ABCs might disturb the cellular immune response to HZ vaccination, which could lower the efficacy of such vaccination in elderly transplant recipients. Full article
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12 pages, 856 KB  
Review
Corticosteroids Contribute to Serious Adverse Events Following Live Attenuated Varicella Vaccination and Live Attenuated Zoster Vaccination
by Nathan B. Price and Charles Grose
Vaccines 2021, 9(1), 23; https://doi.org/10.3390/vaccines9010023 - 6 Jan 2021
Cited by 16 | Viewed by 5816
Abstract
Corticosteroids, when given in high dosages, have long been recognized as a risk factor for severe infection with wild-type varicella-zoster virus in both children and adults. The goal of this review is to assess the degree to which both low-dosage and high-dosage corticosteroids [...] Read more.
Corticosteroids, when given in high dosages, have long been recognized as a risk factor for severe infection with wild-type varicella-zoster virus in both children and adults. The goal of this review is to assess the degree to which both low-dosage and high-dosage corticosteroids contribute to serious adverse events (SAEs) following live varicella vaccination and live zoster vaccination. To this end, we examined multiple published reports of SAEs following varicella vaccination (VarivaxTM) and zoster vaccination (ZostavaxTM). We observed that five of eight viral SAEs following varicella vaccination, including two deaths, occurred in children receiving corticosteroids, while one of three fatal viral SAEs following live zoster vaccination occurred in an adult being treated with low-dosage prednisone. The latter death after live zoster vaccination occurred in a 70 year-old man with rheumatoid arthritis, being treated with prednisone 10 mg daily. Thus, corticosteroids contributed to more severe infectious complications in subjects immunized with each of the two live virus vaccines. Further, when we surveyed the rheumatology literature as well as individual case reports, we documented examples where daily dosages of 7.5–20 mg prednisone were associated with increased rates of severe wild-type varicella-zoster virus infections in children and adults. Full article
(This article belongs to the Special Issue Treatment of Orthopoxvirus Infections)
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19 pages, 3863 KB  
Article
Recombinant Glycoprotein E of Varicella Zoster Virus Contains Glycan-Peptide Motifs That Modulate B Cell Epitopes into Discrete Immunological Signatures
by Rickard Nordén, Jonas Nilsson, Ebba Samuelsson, Christian Risinger, Carina Sihlbom, Ola Blixt, Göran Larson, Sigvard Olofsson and Tomas Bergström
Int. J. Mol. Sci. 2019, 20(4), 954; https://doi.org/10.3390/ijms20040954 - 22 Feb 2019
Cited by 27 | Viewed by 10567
Abstract
A recombinant subunit vaccine (Shingrix®) was recently licensed for use against herpes zoster. This vaccine is based on glycoprotein E (gE) of varicella zoster virus (VZV), the most abundantly expressed protein of VZV, harboring sites for N- and O-linked glycosylation. The [...] Read more.
A recombinant subunit vaccine (Shingrix®) was recently licensed for use against herpes zoster. This vaccine is based on glycoprotein E (gE) of varicella zoster virus (VZV), the most abundantly expressed protein of VZV, harboring sites for N- and O-linked glycosylation. The subunit vaccine elicits stronger virus-specific CD4+ T cell response as well as antibody B cell response to gE, compared to the currently used live attenuated vaccine (Zostavax®). This situation is at variance with the current notion since a live vaccine, causing an active virus infection, should be far more efficient than a subunit vaccine based on only one single viral glycoprotein. We previously found gE to be heavily glycosylated, not least by numerous clustered O-linked glycans, when it was produced in human fibroblasts. However, in contrast to Zostavax®, which is produced in fibroblasts, the recombinant gE of Shingrix® is expressed in Chinese hamster ovary (CHO) cells. Hence, the glycan occupancy and glycan structures of gE may differ considerably between the two vaccine types. Here, we aimed at (i) defining the glycan structures and positions of recombinant gE and (ii) identifying possible features of the recombinant gE O-glycosylation pattern contributing to the vaccine efficacy of Shingrix®. Firstly, recombinant gE produced in CHO cells (“Shingrix situation”) is more scarcely decorated by O-linked glycans than gE from human fibroblasts (“Zostavax situation”), with respect to glycan site occupancy. Secondly, screening of immunodominant B cell epitopes of gE, using a synthetic peptide library against serum samples from VZV-seropositive individuals, revealed that the O-linked glycan signature promoted binding of IgG antibodies via a decreased number of interfering O-linked glycans, but also via specific O-linked glycans enhancing antibody binding. These findings may, in part, explain the higher protective efficacy of Shingrix®, and can also be of relevance for development of subunit vaccines to other enveloped viruses. Full article
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19 pages, 349 KB  
Review
Animal Models of Varicella Zoster Virus Infection
by Kristen Haberthur and Ilhem Messaoudi
Pathogens 2013, 2(2), 364-382; https://doi.org/10.3390/pathogens2020364 - 13 May 2013
Cited by 31 | Viewed by 10895
Abstract
Primary infection with varicella zoster virus (VZV) results in varicella (chickenpox) followed by the establishment of latency in sensory ganglia. Declining T cell immunity due to aging or immune suppressive treatments can lead to VZV reactivation and the development of herpes zoster (HZ, [...] Read more.
Primary infection with varicella zoster virus (VZV) results in varicella (chickenpox) followed by the establishment of latency in sensory ganglia. Declining T cell immunity due to aging or immune suppressive treatments can lead to VZV reactivation and the development of herpes zoster (HZ, shingles). HZ is often associated with significant morbidity and occasionally mortality in elderly and immune compromised patients. There are currently two FDA-approved vaccines for the prevention of VZV: Varivax® (for varicella) and Zostavax® (for HZ). Both vaccines contain the live-attenuated Oka strain of VZV. Although highly immunogenic, a two-dose regimen is required to achieve a 99% seroconversion rate. Zostavax vaccination reduces the incidence of HZ by 51% within a 3-year period, but a significant reduction in vaccine-induced immunity is observed within the first year after vaccination. Developing more efficacious vaccines and therapeutics requires a better understanding of the host response to VZV. These studies have been hampered by the scarcity of animal models that recapitulate all aspects of VZV infections in humans. In this review, we describe different animal models of VZV infection as well as an alternative animal model that leverages the infection of Old World macaques with the highly related simian varicella virus (SVV) and discuss their contributions to our understanding of pathogenesis and immunity during VZV infection. Full article
(This article belongs to the Special Issue Pathogen Infection Models)
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