Herpes zoster (HZ), or shingles, results from the reactivation of latent varicella zoster virus (VZV) [1]. It is characterized by a painful unilateral vesicular rash and can lead to debilitating chronic complications, such as postherpetic neuralgia (PHN) [2, 3]. Everyone infected with VZV is at risk of developing HZ, particularly older adults and immunocompromised patients, due to the decline in cellular immunity, which potentiates virus reactivation [1, 3]. In the USA, 99.5% of adults aged ≥ 40 years show serological evidence of VZV infection, and one in three people will develop HZ during their lifetime [3]. In Europe, the seroprevalence for anti-VZV antibodies ranges from 95.3 to 100% in people aged < 65 years [4]. Furthermore, in adults aged ≥ 50 years, HZ cumulative incidence in Europe and North America is 6.77 and 7.33 per 1000 people, respectively [5]. This highlights the importance of HZ prevention through vaccination, particularly after the COVID-19 pandemic, as individuals aged ≥ 50 years diagnosed with COVID-19 seem to be at higher HZ risk [6].

In Europe, two HZ vaccines are available: the recombinant vaccine (RZV) [7] and the live attenuated vaccine (ZVL) [8]. RZV is indicated for prevention of HZ and PHN in adults aged ≥ 50 years and in adults aged ≥ 18 years at increased HZ risk [7]. The vaccination schedule consists of an initial dose and a second dose 2–6 months later [7]. The ZOE-50 trial demonstrated the efficacy of RZV against HZ (97.2%; 95% confidence interval [CI] 93.7–99.0) and PHN (100%; 95% CI 77.1–100) in individuals aged ≥ 50 years [7, 9, 10]. Specifically, RZV efficacy against HZ was 96.6% (95% CI 89.6–99.4) in those aged 50–59 years and 97.4% (95% CI 90.1–99.7) in those aged 60–69 years. In the pooled analysis of ZOE-50 and ZOE-70 studies, RZV showed an efficacy of 91.3% (95% CI 86.8–94.5) and 88.8% (95% CI 68.7–97.1) against HZ and PHN, respectively, in individuals aged ≥ 70 years [7, 9]. The efficacy of RZV against HZ was sustained for at least 10 years in adults aged ≥ 50 years (89.0%; 95% CI 85.6–91.3) [11]. Grade 3 adverse events (AEs) were more frequent in RZV recipients than in placebo recipients, whereas the proportion of participants who experienced severe AEs or potential immune-mediated diseases (pIMDs) or who died was similar between groups [9, 10]. In adults aged ≥ 50 years, the most frequently reported AEs were pain at the injection site, myalgia, fatigue, and headache; most of these reactions were not long lasting [7]. In immunocompromised individuals aged ≥ 18 years, the safety profile was consistent with that observed in adults aged ≥ 50 years [7]. Important potential risks of RZV include pIMDs, Guillain–Barré syndrome, and virus reactivation in individuals with a history of HZ [12].

ZVL is indicated for prevention of HZ and PHN in adults aged ≥ 50 years, but it is contraindicated in immunocompromised individuals [8]. It is administered in a single dose. ZVL showed an efficacy against HZ of 70% (95% CI 54–81) in people aged 50–59 years, 64% (95% CI 56–71) in those aged 60–69 years, and 38% (95% CI 25–48) in those aged ≥ 70 years (ZEST and SPS trials) [8, 13, 14]. The efficacy of ZVL against PHN was 67% (95% CI 43–81) in a population aged ≥ 70 years [8, 13]. At 10 years post-vaccination, ZVL efficacy significantly declined to 21% (95% CI 11–30) [8, 15]. Injection site reactions were more frequent in the ZVL group than in the placebo group and were generally of moderate intensity; the proportion of individuals who had serious AEs was similar between groups [13, 14]. Safety concerns with ZVL included HZ-like or varicella-like rashes, potential transmission of Oka/Merck vaccine virus strain, exposure of immunocompromised individuals, potential central nervous system events, potential for allergic reactions, and exposure during pregnancy [16].

Several countries worldwide have considered that HZ vaccination is a cost-effective strategy compared with no vaccination. In Germany, vaccination with RZV at age 60 years led to an incremental cost-effectiveness ratio of €23,934 per quality-adjusted life-year [17]. In Spain, in people aged 65 years, the estimated cost per quality-adjusted life-year was €6930 for vaccination with RZV and €20,830 for vaccination with ZVL [18]. In the USA, RZV was identified as a cost-effective strategy compared with no vaccination, and it consistently dominated ZVL [19]; similar findings were observed in China [20]. Other countries, such as the Netherlands [21] and Sweden [22] have not found HZ vaccination to be cost effective. It is noteworthy that cost-effectiveness thresholds depend on the national context of each country and that health problems compete for funding where economic resources are limited. In the specific case of vaccination, vaccines compete for access to reimbursement and inclusion in the national vaccination program based on an assessment of their efficacy, safety, duration of protection, cost effectiveness, and availability, as well as the disease burden, public health impact, economic situation, healthcare infrastructure, or policy support. In some European countries, HZ vaccination is not included in the national vaccination programs, and there are no guidelines from either the bodies responsible for immunization or scientific societies, as was the case in Portugal until recently [23]. This gap led the Portuguese Society of Internal Medicine (SPMI) and the Portuguese Association of General and Family Medicine (APMGF) to issue specific recommendations for HZ vaccination in Portugal [23]. The present work summarizes the availability and reimbursement of HZ vaccines in European countries with recommendations for HZ immunization: Austria [24, 25], Belgium [26, 27], Czechia [24, 28], Denmark [29], France [30,31,32], Germany [33, 34], Greece [24, 35], Ireland [36], Italy [37], Luxembourg [38,39,40], the Netherlands [21, 41], Norway [42,43,44], Poland [45, 46], Portugal [23], Slovenia [47], Spain [18, 48, 49], Sweden [22, 50], Switzerland [51, 52], and the UK [53, 54]. We also highlight the Portuguese guidelines [23] as part of a paradigm shift in the recommendations for HZ vaccination toward a more comprehensive definition of high-risk groups, including individuals with chronic diseases, apart from immunocompromised patients and older adults.

We provide evidence for HZ vaccination of special populations and to expand the number of individuals covered by immunization programs to prevent HZ and its complications in populations at higher risk. We believe that defining vaccination priorities will facilitate the rational inclusion of HZ vaccines in national immunization programs. We also aim to inspire other countries and scientific societies to follow the example of Portugal regarding vaccination against HZ and other diseases for which vaccines have been developed but recommendations do not yet exist.

Table 1 summarizes the availability and reimbursement of HZ vaccines in European countries that have recommendations for HZ immunization. RZV is available in all countries listed here, whereas ZVL is available in all countries except Austria [25], Belgium [27], Czechia [28], Denmark [29], Luxembourg [38], Poland [46], and Slovenia [47] (similarly to the USA, where ZVL is no longer available [55]). Although ZVL is still available until stocks deplete, it has been discontinued in several European countries, including France [30], Norway [43], Portugal [56], and the UK [54]. RZV is the preferred vaccine for the general population in 9/12 countries where both vaccines are available: France [31], Germany [34], Ireland [36], the Netherlands [21], Portugal [23], Spain [18], Sweden [50], Switzerland [52], and the UK [54]. The higher efficacy of RZV compared with ZVL, including in the long term [11], is the main rationale for preferential recommendation, although no head-to-head trials have compared both vaccines. In countries without a preferred vaccine for the general population (3/12), the criteria for RZV or ZVL selection are not specified; patient preference and adherence may affect the choice of the vaccine, as RZV requires two doses and ZVL one dose [7, 8]. In severely immunocompromised individuals, RZV is the only recommended vaccine in all countries, since ZVL is contraindicated in these patients [8]. RZV is reimbursed for specific groups in 13/19 countries and ZVL in 5/12 countries.

The recommendations for HZ vaccination in European countries differ according to both the age of the general population cohort and the definition of individuals at increased HZ risk. In the general population, RZV and ZVL are indicated for prevention of HZ and PHN in adults aged ≥ 50 years, according to the summary of product characteristics (SPCs) [7, 8]. In line with this indication, Czechia [28], Denmark [29], Norway [43], Poland [46], and Portugal [23] consider 50 years the cut-off for recommending vaccination in the general population, as people over this age have a considerably higher risk of developing HZ and PHN [2]. Moreover, HZ vaccines have proven efficacy in this age group [7, 8, 10, 14]. The cut-off is 60 years in Austria [25], Belgium [27], Germany [34], Greece [35], the Netherlands [21], and Slovenia [47]. In France [31], Ireland [36], Italy [37], Luxembourg [39], Spain [18], Sweden [50], Switzerland [52], and the UK [54], the cut-off for vaccination is 65 years. These differences reflect other factors considered by national recommending bodies (e.g. country- and age-specific VZV epidemiology, availability of vaccines, cost-effectiveness analysis) [60].

The definition of groups at increased HZ risk among young people also differs across countries. Several national guidelines consider that young people at higher risk of HZ and complications are immunocompromised but do not further quantify specific risk groups. Other countries, such as Ireland [36], the Netherlands [21], Spain [18], and the UK [54], detail risk groups but restrict them to classical immunocompromised patients (due to illness or treatment). Austria [25], Czechia [28], Germany [34], Italy [37], Poland [46], Portugal [23], Slovenia [47], and Switzerland [52] have more comprehensive definitions of risk groups in young people, including both classical immunocompromised patients and those with chronic diseases that confer some degree of immunosuppression. Remarkably, a meta-analysis reported a significant increase in the relative risk (RR) of HZ for people with chronic obstructive pulmonary disease (COPD; RR 1.41; 95% CI 1.28–1.55), diabetes mellitus (RR 1.24; 95% CI 1.14–1.35), asthma (RR 1.24; 95% CI 1.16–1.31), chronic kidney disease (RR 1.29; 95% CI 1.10–1.51), cardiovascular disease (RR 1.34; 95% CI 1.17–1.54), or inflammatory bowel disease (RR 1.32; 95% CI 1.24–1.40) [61]. The presence of medical conditions at enrollment (e.g. respiratory disorders, diabetes mellitus, asthma, kidney disorders, coronary heart disease) did not influence the efficacy and safety of RZV [62]. Hence, the recommendation for HZ vaccination in individuals with chronic diseases is supported by evidence showing not only their increased HZ risk but also the efficacy and safety of RZV in these groups.

In Portugal, 97.4% of people aged 45–64 years show serological evidence of VZV infection [63]; the incidence of HZ is unknown. Until recently, there were no guidelines for HZ vaccination in the country from either the bodies responsible for immunization or scientific societies. This gap motivated the SPMI and the APMGF, two Portuguese medical societies that cover a large part of the population eligible to receive an HZ vaccine, to set up a working group and publish a consensus report on HZ vaccination [23], before the discontinuation of ZVL in Portugal as of June 2024 [48]. Our article was one of the publications with the most views and downloads in the journal Medicina Interna in 2023 [64]. We recommended HZ vaccination for everyone aged ≥ 50 years and for those aged 18–49 years at high HZ risk [23], including those with the following conditions.

1. a.Medical comorbidities: COPD, diabetes mellitus, bronchial asthma, chronic kidney disease, cardiovascular disease, inflammatory bowel disease, chronic liver disease
2. b.Natural immunosuppression: rheumatoid arthritis, systemic lupus erythematosus, inflammatory myopathies, systemic sclerosis, other systemic autoimmune diseases, HIV infection with CD4 T-cell count ≥ 200 cells/mm³, congenital or acquired immunodeficiency
3. c.Iatrogenic immunosuppression: chronic corticotherapy; synthetic, target, or biological disease-modifying antirheumatic drugs; stem-cell or solid organ transplantation (transplanted or awaiting); hemato-oncologic or oncologic disease.

Our recommendations were based on the evidence that the following are risk factors for developing HZ: older age (RR 1.65; 95% CI 1.37–1.97), medical comorbidities (RR 1.24; 95% CI 1.14–1.35 in patients with diabetes; 1.41; 95% CI 1.28–1.55 in those with COPD; see the section, “Overview of national recommendations across European countries”), and immunosuppression (rheumatoid arthritis, RR 1.51; 95% CI 1.31–1.75; systemic lupus erythematosus, RR 2.08; 95% CI 1.56–2.78; HIV, RR 3.22; 95% CI 2.40–4.33; and malignancies, RR 2.17; 95% CI 1.86–2.53) [61]. Furthermore, RZV has proven efficacy against HZ in these risk groups (≥ 50 years: 97.2%; 95% CI 93.7–99.0 [7, 10]; medical comorbidities: 84.5%; 95% CI 46.4–97.1 in participants with respiratory disorders to 97.0%; 95% CI 82.3–99.9 in those with coronary heart disease [62]; immunosuppression: 68.2%; 95% CI 55.5–77.6 in hematopoietic stem-cell transplantation recipients to 90.5%; 95% CI 73.5–97.5 in participants with pre-existing pIMDs [7, 65,66,67]).

Given the high efficacy of RZV in older adults [7, 9, 10] and those with medical conditions at baseline [62], and its long-term sustained efficacy [11], we advised that immunocompetent individuals should be preferentially immunized with RZV, although ZVL could be considered in exceptional situations (RZV unavailability; serious AE that contraindicates RZV; hypersensitivity to active substances or any excipient of RZV) [23]. Immunocompromised individuals should only be immunized with RZV, since ZVL is contraindicated in this population [8]. We also recommended vaccination of individuals with a previous HZ episode (after at least 1 year since resolution of symptoms) and vaccination with RZV in individuals previously immunized with ZVL (after an interval of at least 1 year) [23].

Our broader definition of high-risk groups for HZ in young people allows for the inclusion of many people with chronic diseases that might have some degree of immunosuppression, in addition to classical immunocompromised patients. Therefore, we extend HZ vaccination to people otherwise not covered by it but who have a substantial risk of developing HZ and in whom RZV is effective and safe [61, 62]. The example of Portugal and other countries [25, 28, 34, 37, 46, 47, 52] constitutes a paradigm shift in the recommendations for HZ vaccination, which could contribute to reduce HZ-associated morbidity, improve patient quality of life, and reduce health costs related to this disease. Defining risk groups and vaccination priorities, as in our recommendations, could also help policymakers and the bodies responsible for immunization and for reimbursement to select who should have priority access to HZ vaccine (free or higher reimbursement). From our perspective, this approach would facilitate the rational inclusion of an HZ vaccine in national immunization programs. It is noteworthy that the Portuguese Vaccination Program mainly focuses on children [68], even though Portugal is one of the European countries with the highest proportion of older adults [69]. In Portugal, as in other countries, there are competing health problems and limited economic resources. Therefore, the inclusion of an HZ vaccine in the national vaccination program will depend on careful assessment by regulatory authorities of vaccine efficacy, safety, duration of protection, cost effectiveness, disease burden, public health impact, and economic circumstances.

Additionally, the consensus report of the SPMI and APMGF highlighted that the physician should have an active role in raising patient awareness about the importance of HZ vaccination [23]. Some measures to promote patient literacy and thus improve HZ vaccine uptake include an explanation about the disease, focusing on its high incidence and morbidity, and clarification about available vaccines. Given their proximity to communities and their deep involvement in vaccination campaigns, family nurses and pharmacists in Portugal are also key to enhancing HZ vaccine education in populations at higher risk, including patients with chronic disorders. Therefore, these healthcare professionals should receive adequate training on their role in promoting HZ vaccination according to the guidelines. Public awareness campaigns could also be useful in maximizing the effect of vaccination recommendations.

Although vaccination against HZ is a known effective strategy for prevention of HZ and its complications such as PHN, a large discrepancy in recommendations across Europe persists. Several European countries have published national guidelines defining priority groups for HZ vaccination, with a direct impact on the protection of vulnerable populations and eventually on national reimbursement policies. Notably, the recent Portuguese guidelines reflect a paradigm shift in the recommendations for HZ vaccination toward a broader definition of high-risk groups, including individuals with chronic diseases, apart from immunocompromised patients and older adults. Given the high efficacy of RZV in these populations, and its long-term sustained efficacy, we preferred RZV to ZVL and recommended vaccination with RZV in individuals previously immunized with ZVL.

In our view, the recommending bodies in each country should regularly review the guidelines on HZ immunization, consider the position of scientific societies, and aim to extend vaccination coverage to everyone at higher risk of disease. We believe that the approach of the SPMI and the APMGF could be an example for countries that do not have national recommendations on HZ vaccination and that this methodology could be replicated in other diseases for which new vaccines have been developed but guidelines are lacking. Despite the specificities of each country regarding disease epidemiology and available resources, efforts should be made within the EU to design and audit health policies that ensure that European citizens have access to uniform healthcare interventions, reflecting equal rights and accessibility to healthcare.