Search Results (124)

Type 1 diabetes mellitus (T1DM) is a chronic autoimmune disorder characterized by the destruction of insulin-producing pancreatic beta cells, resulting in lifelong insulin dependence. While genetic susceptibility—particularly human leukocyte antigen (HLA) class II alleles—is a major risk factor, accumulating evidence implicates viral infections as potential environmental triggers in disease onset and progression. This narrative review synthesizes current findings on the role of viral pathogens in T1DM pathogenesis. Enteroviruses, especially Coxsackie B strains, are the most extensively studied and show strong epidemiological and mechanistic associations with beta-cell autoimmunity. Large prospective studies—including Diabetes Virus Detection (DiViD), The environmental determinans of diabetes in the young (TEDDY), Miljøfaktorer i utvikling av type 1 diabetes (MIDIA), and Diabetes Autoimmunity Study in the Young (DAISY)—consistently demonstrate correlations between enteroviral presence and the initiation or acceleration of islet autoimmunity. Other viruses—such as mumps, rubella, rotavirus, influenza A (H1N1), and SARS-CoV-2—have been investigated for their potential involvement through direct cytotoxic effects, immune activation, or molecular mimicry. Interestingly, certain viruses like varicella-zoster virus (VZV) and cytomegalovirus (CMV) may exert modulatory or even protective influences on disease progression. Proposed mechanisms include direct beta-cell infection, molecular mimicry, bystander immune activation, and dysregulation of innate and adaptive immunity. Although definitive causality remains unconfirmed, the complex interplay between genetic predisposition, immune responses, and viral exposure underscores the need for further mechanistic research. Elucidating these pathways may inform future strategies for targeted prevention, early detection, and vaccine or antiviral development in at-risk populations. Full article

The varicella-zoster virus is a human herpesvirus that causes varicella as the primary infection and HZ as the reactivation of a latent infection. Ten to twenty percent of cases of herpes zoster ophthalmicus (HZO) involve the ophthalmic branch of the fifth cranial nerve. Any area of the eye may be affected by the condition. HZ has a lifetime risk of more than 30%. Complications from herpes zoster can significantly lower quality of life. The goal of HZ vaccinations is to stop HZ activation and PHN formation. Despite the uncommon possibility of side effects such as eye problems, the majority of vaccines on the market now are safe. The purpose of this review is to discuss VZV infection and analyze and summarize the ocular complications following VZV vaccination. Full article

Background: Immunocompromised patients are at risk of severe varicella zoster virus (VZV) infection and reactivation. In VZV seronegative immunocompromised persons, live-attenuated VZV vaccination is contraindicated, thus the recombinant herpes zoster vaccine (rHZV) remains a safe alternative, although an off-label application. Yet, data on the induction of a VZV-specific immune response in immunocompromised individuals with VZV-specific IgG below the assay’s cut-off are only available for patients after solid-organ transplantation (SOT). Methods: We retrospectively analyzed the induction of VZV-specific IgG antibody levels after vaccination with rHZV in immunocompromised patients who previously tested anti-VZV-IgG negative between March 2018 and January 2024. Results: Of 952 vaccinees screened that received 2 or 3 doses rHZV, depending on the underlying disease, 33 patients (median age 53.0; 51.5% female) with either hematopoietic stem cell transplantation (82%) or high-grade immunosuppressive treatment (18%) fulfilled the inclusion criteria. Upon rHZV vaccination, 88% (29/33) individuals mounted a significant antibody response exceeding the assay’s cut-off level for seropositivity (p < 0.0001). We detected higher geometric mean antibody concentrations after three compared to two doses. However, 12% remained below the assay’s cut-off level and were therefore considered non-responsive. Conclusions: The rHZV is immunogenic in VZV-seronegative immunocompromised individuals and therefore presents a valid option to induce seroconversion. However, antibody testing in high-risk groups should be considered to identify humoral non- and low responders. Full article

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

Understanding the contribution of human herpesviruses to the aetiology of neurodegenerative diseases is an emerging field of interest. The association of Epstein–Barr virus with multiple sclerosis is the most researched example; however, the definitive proof of causation is still lacking. Alzheimer’s disease (AD) is the most common form of dementia and typically manifests in individuals aged over 65 years; however, it also occurs in a small number of individuals aged less than 65 years. A combination of environmental, genetic, and lifestyle factors is believed to contribute to the development of AD. There have been several reports describing potential associations of infections or reactivations of human alphaherpesviruses with AD. A particular characteristic of human alphaherpesviruses (herpes simplex viruses 1 and 2, varicella zoster virus) is that they are neurotropic and that lifelong infection (latency) is established mainly in the dorsal root and trigeminal ganglia. There have also been reports that suppression of alphaherpesvirus infections through either vaccination or the application of antiviral treatments may be protective against the development of AD. Zoster vaccines and acyclovir may prove to be effective interventions for preventing or limiting the progression of AD. This is particularly relevant as there are currently no available cheap and effective treatments for AD. In this review, the basic virology of human alphaherpesviruses is described followed by their epidemiology and associations with AD. Finally, the prevention and treatment of human alphaherpesviruses are considered in the context of potential applications for the prevention of AD. Full article

The varicella vaccine has prevented varicella in hundreds of thousands of patients since its establishment in 1974. It stimulates both humoral and cell-mediated immunity to produce an immune response that helps protect against the disease (not necessarily the infection). Serious sequala of varicella including pneumonia, hepatitis, and encephalitis can occur, with higher incidence in immunosuppressed individuals than in the general population. Patients who are not immunosuppressed should receive routine varicella vaccinations. For those who have not completed the series or are significantly distant from their last immunization, serologic testing may be considered. In pre-transplant patients, live-attenuated vaccines should ideally be administered at least four weeks before transplantation. Case studies have documented instances of patients requiring treatment for varicella after receiving a transplant within four weeks of vaccination. Full article

Background: Alzheimer’s Disease (AD) represents a significant public health challenge with a rising global burden. Emerging evidence suggests a potential link between herpes zoster (HZ) and an increased risk of AD. These findings indicate that HZ may contribute to neuroinflammation and other pathophysiological processes associated with AD, pointing out the potential role of the virus infection in the initiation and/or progression of AD pathology. Objective: This systematic review evaluates the relationships between HZ and the risk of AD, highlighting the potential neuroprotective role of HZ vaccination and antiherpetic drug (AHD) use. Methods: Adhering to the (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) PRISMA guidelines, a comprehensive search of databases (e.g., PubMed) until October 2024 was conducted. Observational studies reporting risk estimates were included. Extracted data were synthesized and analyzed narratively due to study heterogeneity. Results: Eleven studies (out of two hundred) met the inclusion criteria, offering preliminary insights that could form a foundation for further investigation. Reports on HZ showed mixed outcomes, with some studies suggesting a potential increased risk of AD, while others showed no clear correlation. Interestingly, HZ vaccination led to a potential preventive role in reducing the risk of AD, with risk estimates ranging from 0.57 to 0.99. Additionally, the use of AHDs was linked to a reduced risk of AD, with risk estimates ranging from 0.65 to 0.96. Conclusions: Published findings suggest that HZ vaccination and AHD use could represent potential interventions to reduce the risk of AD; however, further research is necessary to validate these findings and better understand the underlying protective mechanisms. Full article

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

Background: Varicella zoster virus (VZV) infection can be life-threatening for fragile and immunosuppressed patients. Recombinant VZ vaccination (RVZV) has been recommended for vulnerable patients to reduce the risk of reactivation. Hemodialysis (HD) patients often have weakened immune systems and a high prevalence of comorbidities, which may justify the use of RVZV. This study examines the difference in VZ antibody levels following RVZV and its significance in HD patients. Methods: We measured the levels of immunoglobulin G antibodies against VZ (VZ-IgG) in the HD population. We also collected demographic and clinical data for each patient, including their age, length of time on dialysis, Charlson Comorbidity Index (CCI), and markers of nutritional and inflammatory status. Results: A total of 160 patients were evaluated, with 111 (69.4%) male and 143 (89.3%) Caucasian. The mean VZ-IgG levels after one year were significantly higher in patients who received RVZV than those who did not (2177 ± 834 versus 1494 ± 882, p < 0.001). Additionally, among all other risk factors, only CCI harmed the VZ-IgG levels in non-vaccinated HD patients (B −403 with 95%CI −778 −27.9, p = 0.039). Overall, 98.8% of patients were found to be seropositive for VZ, with only one patient in each group (RVZV and non-RVZV) testing negative. Conclusions: Patients who received RVZV showed higher VZ IgG levels after one year compared to those who did not. Moreover, unvaccinated patients with more comorbidities had lower anti-VZ IgG titers. Full article

Background: Respiratory syncytial virus (RSV) and varicella–zoster virus (VZV) pose significant risks to the elderly and individuals with compromised immune systems. In this study, we investigated whether combining RSV and VZV vaccines could reduce the number of vaccination injections, thereby minimizing discomfort for elderly individuals and reducing manufacturing costs. Methods: In this study, we developed two types of combined RSV and VZV mRNA vaccines. Using RSV and VZV mRNA vaccines administered alone as controls, we evaluated the immune response elicited by the combined mRNA vaccines in C57BL/6J mice. Results: The results demonstrated that RSV mRNA, VZV mRNA, and a mixture of both could be effectively encapsulated in lipid nanoparticles (LNPs) with uniform particle sizes. Compared to the administration of either the RSV or VZV mRNA vaccine alone, the delivery of two kinds of mRNA LNP combination formulation—whether directly mixed or encapsulated two mRNAs in the same LNP formulation—elicited comparable IgG titers, neutralization titers, cell-mediated immunity (CMI), and CD4⁺ T-cell responses. Conclusions: In conclusion, this study establishes the feasibility of combining RSV and VZV mRNA-LNP vaccines, laying a solid foundation for clinical trials of combined RSV and VZV vaccines. Full article

Background: Cytomegalovirus (CMV) infection and age impact immune responses to vaccines. The effect of sex remains controversial. We investigated the relationship between cytomegalovirus-seropositivity, age, and sex and the immunogenicity of the recombinant (RZV) and live (ZVL) zoster vaccines in adults ≥50 years of age. Methods: Varicella zoster virus (VZV) glycoprotein E (gE)-specific antibody, antibody avidity, and cell-mediated immunity (CMI) were measured pre-vaccination and at regular intervals over 5 years post-vaccination in 80 RZV and 79 ZVL recipients, including 91 cytomegalovirus-seropositive and 90 female participants. Results: Differences associated with CMV-seropositivity: lower VZV-gE-CMI in RZV recipients after the first dose of vaccine, but no differences after the 2nd dose; lower VZV-gE-specific antibody avidity in ZVL recipients; and more abundant Th1 and senescent T cells (Tsen) and less abundant regulatory (Treg) and tissue-resident memory T cells (Trm). Differences associated with older age: lower antibody responses in RZV recipients and lower Th1 cells. Differences associated with sex: none for immunogenicity of either vaccine. Differences associated with T cell subset abundance: higher Tsens and lower Tregs or Trms were associated with lower post-dose 1 VZV-gE-specific CMI in RZV recipients, and higher Th1s were associated with higher antibody concentrations. Conclusions: The correlation of CMV- and age-associated T cell subsets with the immunogenicity of ZVLs and RZVs suggests that T cell imprinting contributes to the effect of age and CMV on vaccine responses. Full article

Background/Objectives: An overwhelming burden to clinics, herpes zoster (HZ), or shingles, is a painful disease that occurs frequently among aged individuals with a varicella-zoster virus (VZV) infection history. The cause of shingles is the reactivation of dormant VZV in the dorsal root ganglia/cranial nerves of the human body. Patients with HZ experience sharp, intense, electric shock-like pain, which makes their health-related quality of life (HRQoL) extremely low. Methods: Various mRNA constructs were designed based on intracellular organelle-targeting strategies and AI algorithm-guided high-throughput automation platform screening and were then synthesized by in vitro transcription and encapsulated with four-component lipid nanoparticles (LNPs). Immunogenicity was evaluated on a naïve mouse model, long-term mouse model, and VZV-primed mouse model. Safety was evaluated by a modified “nestlet shredding” method for potential adverse effects induced by vaccines. Comparison between muscular and intradermal administrations was conducted using different inoculated approaches as well. Results: The best vaccine candidate, CVG206, showed robust humoral and cellular immune responses, durable immune protection, and the fewest adverse effects. The CVG206 administered intradermally revealed at least threefold higher humoral and cellular immune responses compared to intramuscular vaccination. The manufactured and lyophilized patch of CVG206 demonstrated good thermal stability at 2–8 °C during 9 months of storage. Conclusions: The lyophilized mRNA vaccine CVG206 possesses remarkable immunogenicity, long-term protection, safety, and thermal stability, and its effectiveness could even be further improved by intradermal administration, revealing that CVG206 is a promising vaccine candidate for HZ in future clinical studies. Full article

Background: Herpes zoster (HZ) is a painful neurocutaneous disease caused by the varicella-zoster virus. The recombinant zoster vaccine (RZV) is becoming increasingly incorporated into national vaccination schedules. We aimed to evaluate RZV from a global public health policy perspective. Methods: We performed a rapid review of studies evaluating the immunogenicity, efficacy, and effectiveness of RZV for protection against HZ and associated complications. We searched PubMed for English-language studies published between 7 August 2012 and 30 September 2023. Included studies reported vaccine efficacy or effectiveness against HZ and HZ-associated complications. Immunogenicity studies were included if they contributed to the understanding of RZV protection over time and/or co-administration with other vaccines. HZ outcomes were stratified by socio-demographic and clinical variables. Results: From 405 identified publications, 33 were eligible for the study. Most studies were conducted in the US (N = 12), across North America (N = 10), and Europe (N = 5), or across multiple locations across North America, Latin America, and Asia–Australia (N = 6). Vaccine efficacy against HZ in immunocompetent populations ranged between 90% and 97%, while effectiveness ranged between 71% and 86%. Protection stayed above 70% for at least 10 years, with no significant differences by age or ethnicity. Conclusions: RZV is effective in reducing the risk of HZ and its associated complications. Protection is long-lasting and the vaccine is suitable for older and immunocompromised populations. However, the decision to incorporate the vaccine into national policies depends on additional factors (e.g., cost-effectiveness), which may be difficult to characterize without an understanding of the global disease burden. Full article

Chronic obstructive pulmonary disease (COPD) is often exacerbated by various viruses and bacteria, leading to acute episodes of worsening respiratory symptoms, which contribute significantly to the morbidity and mortality associated with COPD. Consequently, vaccination against these pathogens is recommended by numerous guidelines to safeguard COPD patients from adverse health outcomes. The Global Initiative for Chronic Obstructive Lung Disease (GOLD) recommendation advocates for vaccination against influenza, Streptococcus pneumoniae, respiratory syncytial virus (RSV), severe acute respiratory syndrome coronavirus (SARS-CoV2), pertussis, and varicella zoster. This review article will examine the current vaccination strategies recommended for adult COPD patients and will discuss the clinical benefits associated with these vaccines. Full article

Background: There is scarce information on Varicella–Zoster virus genetic variability in individuals with acute central nervous system infection in Brazil. The objective of this study was the molecular characterization of Varicella–Zoster virus isolates in cerebrospinal fluid from individuals with acute central nervous system infection. Methods: Cerebrospinal fluid samples were collected from individuals evaluated in emergency and community healthcare services in São Paulo, Brazil. Varicella–Zoster virus identification was performed using commercial platforms Biofire-FilmArray Meningitis/Encephalitis (BioMérieux, Craponne, France) and XGEN-UMLTI-N9^® (Mobius Life, Pinhais, Brazil). Positive samples were further characterized as wild-type or vaccine-strain by a real-time polymerase chain reaction assay that targeted a single nucleotide polymorphism in open reading frame 62. We also estimated the mean genetic distance and phylogenetic reconstruction based on open reading frames 22, 38, 54, and 62 in relation to sequences of intercontinentally circulating Varicella–Zoster virus isolates. Results: Among the 600 cerebrospinal fluid samples, we identified Varicella–Zoster virus in 30 (5%) samples. None were positive for the vaccine-strain. Twelve samples were sequenced and phylogenetically classified into Clades 1 (41.7%), 2 (25%), 3 (8.3%), 5 (16.7%), or 6 (8%). Conclusion: Enhanced characterization of circulating Varicella–Zoster virus Clades in Brazil identified previously unreported Clades 2 and 6 as well as three other Clades disseminated intercontinentally. These findings reinforce the importance of Varicella–Zoster virus molecular surveillance in cerebrospinal fluid. Full article