Varicella-zoster virus (VZV) is a neurotropic herpesvirus responsible for varicella and herpes zoster. Beyond its classical clinical manifestations, recent evidence shows that VZV reactivation may contribute to acute cardiovascular events. Vaccination reduces the incidence of herpes zoster and may confer cardiovascular benefits, although causality remains unproven. To summarise current evidence linking VZV infection to cardiovascular risk, evaluate the impact of VZV vaccination in the general and immune-mediated inflammatory disease (IMID) populations, and discuss the hypothesis that increased VZV reactivation under Janus kinase inhibitor (JAKi) therapy may partially explain the major adverse cardiovascular event (MACE) signal observed in the ORAL Surveillance trial. Epidemiologic studies show a consistent association between herpes zoster and a transient increase in MACEs. Mechanistic insights support VZV's ability to infect vascular tissues, induce inflammation, destabilise atherosclerotic plaques, and enhance thrombogenicity. Vaccination with the recombinant zoster vaccine (RZV) effectively prevents herpes zoster and is associated with reduced MACEs in large observational cohorts, although randomised trials powered for cardiovascular endpoints are lacking. In IMID populations, vaccination reduces herpes zoster incidence but has not consistently demonstrated cardiovascular benefit. JAKis, which increase VZV reactivation risk by impairing antiviral immunity, may create episodic vascular insults that contribute to the elevated MACE rates observed with tofacitinib in the ORAL Surveillance trial. VZV reactivation is a plausible and potentially preventable contributor to cardiovascular risk, particularly in older and immunosuppressed individuals. While vaccination shows promise in reducing zoster-associated cardiovascular risk, definitive causal evidence remains lacking. The hypothesised JAKi-VZV-vascular pathway warrants prospective evaluation.

Recombinant adjuvanted herpes zoster vaccine (Shingrix) effectively prevents varicella-zoster virus (VZV) reactivation and is recommended for older and immunocompromised adults.

Background/Objectives: Patients with inflammatory bowel disease (IBD) are at an increased risk of herpes zoster (HZ), particularly during immunosuppressive treatment. To assess the safety of the recombinant zoster vaccine (RZV, Shingrix[®]) and describe HZ occurrence in a real-world IBD cohort, including patients receiving advanced therapies. Methods: This prospective, single-centre observational study included 114 adults with IBD who were offered RZV; 69 received at least one dose, and 45 declined or postponed vaccination. Follow-up began at the vaccine proposal. For time-to-event analyses, vaccination was modelled as a time-varying exposure beginning 14 days after a documented second dose. IBD clinical relapse was defined by worsening disease-activity indices and/or treatment escalation. Results: During a median follow-up of 17 months (IQR 9-29), 11 patient-reported HZ episodes occurred: 8/69 (11.6%) among patients who received vaccination and 3/45 (6.7%) among those who did not. The time-dependent association between complete vaccination and HZ was not statistically significant (HR 2.51; 95% CI 0.66-9.51; p = 0.18), and adjustment for advanced therapy did not materially change the estimate. Prior HZ was associated with a higher risk of a subsequent reported episode (adjusted HR 6.26; 95% CI 1.80-21.76; p = 0.004). IBD clinical relapse occurred in 4/69 (5.8%) vaccinated and 2/45 (4.4%) unvaccinated patients (p = 1.00). Among 72 patients receiving advanced therapy, HZ occurred in 4/42 vaccinated and 2/30 unvaccinated patients (p = 1.00), while IBD relapse occurred in 3/42 and 1/30, respectively (p = 0.64). No serious vaccine-related adverse events or significant pre-/post-vaccination changes in disease activity were observed. Conclusions: RZV showed a favourable short-term safety profile in patients with IBD, including those receiving advanced therapies. The small number of self-reported HZ events and the non-randomised design preclude conclusions regarding vaccine effectiveness.

The global aging population faces heightened vulnerability to infectious diseases due to immunosenescence, which diminishes the potency, durability, and breadth of vaccine-induced immunity. While the leading shingles vaccine, Shingrix, provides protection against herpes zoster virus for adults aged 50 and older, it is often associated with severe local and systemic reactogenicity, which limits vaccine compliance. Here, we report an injectable polymer-nanoparticle (PNP) hydrogel platform for the sustained delivery of a shingles subunit vaccine to enhance immune responses while mitigating reactogenicity in aged mice. Hydrogel-based vaccination elicited significantly more potent and durable humoral immune responses than Shingrix, while inflammatory cytokine levels remained below the limit of detection. Moreover, aged mice vaccinated with the hydrogel-based vaccine exhibited robust antigen-specific cellular immune responses. These findings demonstrate that controlling the temporal presentation of vaccine components can overcome age-associated declines in immune responsiveness without inducing excessive inflammatory signaling. By decoupling immunogenicity from reactogenicity, our hydrogel-based delivery strategy offers a promising approach to improve both the efficacy and tolerability of subunit vaccines for the elderly and may be broadly applicable to other vaccines targeting aging populations.

A 77-year-old woman was being treated for rheumatoid arthritis with prednisolone, methotrexate, and iguratimod. The patient was administered a live-attenuated varicella vaccine (Oka strain) for herpes zoster prevention by a primary care physician. Four weeks later, a vesicular rash appeared on the body. The patient was treated with amenamevir, and the rash improved. Based on the pathological findings and viral genotyping, she was diagnosed with a vaccine-induced disseminated varicella-zoster virus infection. For herpes zoster vaccination, caution is warranted as some medical questionnaires for vaccination do not include glucocorticoid use or immunosuppressive therapy, and some primary care physicians administer live vaccines only.

Vaccines based on purified antigens, recombinant proteins, and nucleic acid platforms increasingly depend on adjuvants to induce robust, durable, and appropriately polarized immune responses in humans. While classical adjuvants such as aluminum salts and oil-in-water emulsions have enabled the success of many licensed vaccines, their largely empirical design limits adaptability to emerging pathogens and population-specific needs. This review presents a translational framework for next-generation vaccine adjuvant development by integrating nanotechnology-based delivery systems, innate immune signaling mechanisms, and systems-level computational strategies relevant to human vaccination. We summarize the mechanisms and clinical relevance of licensed and advanced adjuvants, including alum, MF59, AS01/AS04, saponins, toll-like receptor agonists, and lipid nanoparticles, with emphasis on influenza, HPV, herpes zoster, and COVID-19 vaccines. By linking immunological mechanisms with delivery engineering and predictive modeling, this review highlights rational strategies to support safer and more effective human vaccines.

We studied current vaccination policies for health-care personnel (HCP) in 34 European countries. All (34) countries have vaccination policies for hepatitis B, 33 countries for influenza, and 22 countries for COVID-19. Vaccination policies for measles, mumps, rubella, and varicella exist in 28, 23, 24, and 26 countries, respectively, and for tetanus, diphtheria, pertussis, and poliomyelitis in 21, 23, 23, and 15 countries, respectively. Vaccination policies for hepatitis A exist in 20 countries, and for tuberculosis (BCG vaccine), pneumococcus, herpes zoster, and human papillomavirus in 6, 6, 2, and 1 country, respectively. Lastly, 16 countries have vaccination policies for meningococcus B, 4 for meningococcus C, and 19 for meningococci ACWY (quadrivalent vaccine). Sixteen countries mandate particular vaccinations for HCP (mainly against hepatitis B and measles), including nine as a prerequisite for employment. Comparing the current vaccination policies with those we reported in 2018, we found that on several occasions vaccination programs improved and include an average of four more vaccinations. However, in several countries there are gaps in vaccination policies, particularly against measles, mumps, rubella, varicella, and pertussis. Currently, most countries have vaccination recommendations for healthcare students before entering healthcare facilities. In conclusion, European countries have more comprehensive vaccination policies for HCP compared with 2018, however there are still significant differences between countries, in terms of the number of vaccinations, target personnel, and implementation frame (recommended or mandatory vaccinations). Given the resurgence of multiple vaccine-preventable diseases in recent years, evidence-based and harmonized vaccination policies for HCP in Europe are needed to protect HCP and patients and to enhance safety in healthcare facilities.

Herpesviruses employ sophisticated immune evasion strategies to establish lifelong infections, subverting type I interferon (IFN-I) responses critical for antiviral defense. However, their adaptive mechanisms across species remain poorly characterized. Using duck plague virus (DPV)-an avian alphaherpesvirus model-we identify a cooperative immune evasion axis wherein ICP27 orchestrates UL55-mediated immunosuppression through dual regulatory mechanisms: its RNA-binding domain (RGG) facilitates UL55 mRNA nuclear export, while its C-terminal domain (CTD) stabilizes UL55 protein via direct interaction. This partnership enables synergistic suppression of IFN-I signaling-co-expression of ICP27 and UL55 inhibits Poly(I:C)-induced immune genes (IFN-β, Mx, OASL, IL-6) more potently than either protein alone. UL55 functions as a precision-targeted IFN-I antagonist, selectively degrading RIG-I and IRF7 through proteasomal pathways-confirmed by proteasome inhibitor rescue (MG132), structural modeling (AlphaFold), and binding assays (Co-IP). Evolutionarily, UL55 homologs (DPV, Herpes simplex virus type 1 [HSV-1], Varicella zoster virus [VZV]) conserve RIG-I targeting but diverge in IRF3/IRF7 regulation-adaptations shaped by UL55 sequence divergence (38.68% identity) and host biology (e.g., waterfowl IRF3 deficiency). This work establishes ICP27-UL55 as a key regulatory axis in herpesviral immune evasion and redefines UL55 as a conserved yet adaptable immunosuppressor in Alphaherpesvirinae.IMPORTANCEThis study fundamentally advances herpesvirology by defining a novel immune evasion paradigm in duck plague virus. We reveal ICP27 as a master regulator that coordinates UL55 immunosuppression through a two-tiered mechanism: RGG domain-mediated mRNA nuclear export and CTD-dependent protein stabilization-an unreported strategy in herpesviruses. UL55 selectively degrades RIG-I and IRF7 via proteasomal pathways, enabling precise IFN-I suppression with minimal immune activation. Crucially, ICP27-UL55 synergy inhibits Poly(I:C)-induced immune genes (IFN-β, Mx, OASL, IL-6) more effectively than individual proteins. Evolutionary analyses demonstrate conserved targeting of RIG-I across alphaherpesvirus UL55 homologs (DPV, HSV-1, VZV) but host-adapted divergence in IRF3/IRF7 regulation, shaped by UL55 sequence variation (38.68% identity) and host biology (e.g., avian IRF3 deficiency). These findings provide the first evidence of effector coordination through integrated transcriptional/post-translational regulation in herpesviruses. Disrupting ICP27-UL55 interaction offers new antiviral targets, while UL55-deficient strains serve as vaccine candidates for poultry disease control.