Search Results (173)

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

Background/Objectives: The aetiology of Bell’s palsy remains unclear and is typically diagnosed by exclusion. This study investigated the potential role of neurotropic viruses and explored the relationship between facial nerve impairment and vestibular dysfunction to improve the understanding of the condition. Methods: Antibodies against herpes simplex virus (HSV) and varicella-zoster virus (VZV) were assessed using ELISA. Vestibular function was evaluated through computerised videonystagmography, rotatory chair, and clinical vestibulospinal assessments. Facial nerve lesion localisation was determined by stapedial reflex testing. Fisher’s exact test was used for statistical analysis. Results: Of 51 patients with Bell’s palsy, 62.7% exhibited vestibular dysfunction, and 70.6% were IgG-positive for at least one neurotropic virus. Vestibular impairment was significantly more common in seropositive patients. Statistically significant associations were observed between vestibular dysfunction and viral IgG seropositivity (p < 0.0001), the severity of vestibular dysfunction and facial paresis (p = 0.0126), and the side of vestibular impairment and the side of facial palsy (p < 0.0001), with 90.6% of cases showing ipsilateral involvement. Conclusions: These findings support the hypothesis that neurotropic viruses may act as a common pathological factor in both Bell’s palsy and associated vestibular dysfunction. 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

Rapid, safe, and field-deployable molecular diagnostics are crucial for the effective management of infectious disease outbreaks, particularly those involving highly infectious pathogens, which can produce clinical symptoms similar to less infectious pathogens, thus raising potential biosafety concerns. In this study, we evaluated DNA/RNA Defend Pro (DRDP) buffer, a novel viral-inactivating transport medium designed to stabilize nucleic acids and allow direct PCR without nucleic acid extraction. To ensure critical qPCR parameters were not compromised by using DRDP, we conducted serial dilution tests using herpes simplex viruses 1 and 2 (HSV-1, HSV-2) and varicella-zoster virus (VZV), comparing DRDP to standard universal transport medium (UTM). Detection sensitivity, determined by cycle quantification (Cq) values, favored DRDP, as UTM samples required a 2–3-fold dilution to mitigate PCR inhibition. DRDP maintained reliable PCR compatibility at reaction volumes containing up to 25% buffer. At higher DRDP concentrations (30–35%), PCR inhibition occurred due to EDTA content but was fully reversible by adding supplemental magnesium. Furthermore, DRDP samples did not require an initial 95 °C thermal lysis step, thus simplifying the procedure without reducing PCR sensitivity or efficiency. 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

Purpose: Varicella zoster virus (VZV) vasculopathy can occur in patients with herpes zoster (HZ). Our aim was to evaluate the retinal microvascular vessel density (VD) in patients with trigeminal HZ measured by optical coherence tomography angiography (OCTA). Methods: 48 eyes of 24 patients with HZ and 48 eyes of 24 healthy age- and gender-matched controls were included in this study. All participants underwent an OCTA examination using RTVue XR Avanti with AngioVue. The VD data of the macular 3 × 3 mm OCT angiogram of the superficial capillary plexus (SCP), the deep capillary plexus (DCP), and the choriocapillaris (CC) as well as the VD data of the optic nerve head (ONH) were extracted and analyzed. Results: The VD in the SCP, DCP, and CC of patients with HZ was significantly lower compared with healthy controls (p < 0.05). Equally, there was a noticeable reduction in the inside disk area of the ONH. There was no statistically noticeable reduction in the FAZ area and central retinal thickness. Conclusions: In this study, HZ patients demonstrated a decrease in the retinal VD of the SCP, DCP, ONH, and the CC. Quantitative analysis of retinal perfusion using OCTA may therefore help in the diagnosis and monitoring of HZ. Further studies must show to what extent this may be an indication of VZV-related vasculopathy and whether OCTA data can be used as a biomarker in these patients in the future. 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

Corneal endotheliitis is an inflammatory process, most commonly of viral etiology, that manifests clinically with features including corneal edema, keratic precipitates, and a mild anterior chamber reaction. Several studies have implicated human herpesviruses from the Herpesviridae family as primary causes of corneal endotheliitis, including cytomegalovirus (CMV), varicella zoster virus (VZV), and herpes simplex viruses 1 and 2 (HSV-1 and HSV-2). This review critically evaluates the present literature surrounding herpesvirus infections of the corneal endothelium. 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

Dermatological vaccines have emerged as critical tools in preventing and managing a wide spectrum of skin conditions ranging from infectious diseases to malignancies. By synthesizing evidence from existing literature, this review aims to comprehensively evaluate the efficacy, safety, and immunogenicity of vaccines used in dermatology, including both approved vaccines and those currently being researched. Vaccines discussed in this paper include those targeting dermatoses and malignancies (e.g., acne vulgaris, atopic dermatitis, and melanoma); infectious diseases (e.g., human papillomavirus (HPV); varicella zoster virus (VZV); herpes zoster (HZ); warts; smallpox; mpox (monkeypox); hand, foot, and mouth disease (HFMD); candidiasis and Group B Streptococcus (GBS); and neglected tropical diseases (e.g., Buruli ulcer, leprosy, and leishmaniasis). Through this review, we aim to provide a detailed understanding of the role of vaccines in dermatology, identify knowledge gaps, and propose areas for future research. Full article

Background/Objectives: Approved mRNA vaccines commonly use sequences modified with pseudouridine to enhance translation efficiency and mRNA stability. However, this modification can result in ribosomal frameshifts, reduced immunogenicity, and higher production costs. This study aimed to explore the potential of unmodified mRNA sequences for varicella-zoster virus (VZV) and evaluate whether codon optimization could overcome the limitations of pseudouridine modification. Methods: We utilized artificial intelligence (AI) to design several unmodified gE mRNA sequences for VZV, considering factors such as codon preference and secondary structure. The optimized mRNA sequences were assessed for protein expression levels in vitro and were subsequently used to develop a vaccine, named Vac07, encapsulated in a lipid nanoparticle (LNP) delivery system. The immunogenicity of Vac07 was evaluated in mice. Results: Codon-optimized mRNA sequences showed significantly higher protein expression levels in vitro compared to wild-type (WT) sequences. Vaccination with Vac07 demonstrated immunogenicity in mice that was comparable to, or even superior to, the licensed Shingrix vaccine, characterized by a stronger Th1-biased antibody response and a slightly more robust Th1-type cellular response. Conclusions: Codon-optimized unmodified mRNA sequences may also represent a viable approach for mRNA vaccine development. These optimized sequences have the potential to lower production costs while possibly enhancing the immunogenicity of mRNA vaccines. Vac07, developed using this method, shows promise as a potentially more efficient and cost-effective mRNA vaccine candidate for VZV. Full article