RESUMEN
Herpes zoster is a viral infection caused due to the reactivation of varicella-zoster virus that is localized to a single dermatome unilaterally. The factors responsible for its reactivation are increasing age, immunosuppressive drugs, malignancies, chronic liver and renal diseases. Herpes zoster was found to be one of the cutaneous manifestations of coronavirus disease 2019 (Covid-19). Various skin manifestations post-vaccination are being reported, which include injection site urticarial, maculopapular rash and positive dermographism. We report a patient of herpes zoster triggered by the viral vector (ChAdOx1 nCoV-19) coronavirus vaccine (recombinant).
Asunto(s)
Vacunas contra la COVID-19 , COVID-19 , ChAdOx1 nCoV-19 , Herpes Zóster , Humanos , Herpes Zóster/prevención & control , Herpes Zóster/inmunología , Vacunas contra la COVID-19/efectos adversos , Vacunas contra la COVID-19/administración & dosificación , COVID-19/prevención & control , COVID-19/inmunología , Masculino , SARS-CoV-2/inmunología , Persona de Mediana Edad , FemeninoRESUMEN
Background: Currently, evidence regarding the causal relationship between primary immunodeficiency-related genes and varicella-zoster virus reactivation syndrome is limited and inconsistent. Therefore, this study employs Mendelian randomization (MR) methodology to investigate the causal relationship between the two. Methods: This study selected 110 single-nucleotide polymorphisms (SNPs) of primary immunodeficiency-related genes as instrumental variables (IVs). Genetic associations of primary immunodeficiency-related genes were derived from recent genome-wide association studies (GWAS) data on human plasma protein levels and circulating immune cells. Data on genes associated with varicella-zoster virus reactivation syndrome were obtained from the GWAS Catalog and FINNGEN database, primarily analyzed using inverse variance weighting (IVW) and sensitivity analysis. Results: Through MR analysis, we identified 9 primary immunodeficiency-related genes causally associated with herpes zoster and its subsequent neuralgia; determined causal associations of 20 primary immunodeficiency-related genes with three vascular lesions (stroke, cerebral aneurysm, giant cell arteritis); revealed causal associations of 10 primary immunodeficiency-related genes with two ocular diseases (retinopathy, keratitis); additionally, three primary immunodeficiency-related genes each were associated with encephalitis, cranial nerve palsy, and gastrointestinal infections. Conclusions: This study discovers a certain association between primary immunodeficiency-related genes and varicella-zoster virus reactivation syndrome, yet further investigations are warranted to explore the specific mechanisms underlying these connections.
Asunto(s)
Estudio de Asociación del Genoma Completo , Herpesvirus Humano 3 , Análisis de la Aleatorización Mendeliana , Polimorfismo de Nucleótido Simple , Humanos , Herpesvirus Humano 3/inmunología , Herpes Zóster/genética , Herpes Zóster/inmunología , Herpes Zóster/virología , Activación Viral , Enfermedades de Inmunodeficiencia Primaria/genética , Enfermedades de Inmunodeficiencia Primaria/inmunología , Predisposición Genética a la Enfermedad , Infección por el Virus de la Varicela-Zóster/genética , Infección por el Virus de la Varicela-Zóster/inmunología , Síndromes de Inmunodeficiencia/genéticaRESUMEN
Mucosal-associated invariant T (MAIT) cells are unconventional T cells that respond to riboflavin biosynthesis and cytokines through TCR-dependent and -independent pathways, respectively. MAIT cell activation plays an immunoprotective role against several pathogens, however the functional capacity of MAIT cells following direct infection or exposure to infectious agents remains poorly defined. We investigated the impact of Varicella Zoster Virus (VZV) on blood-derived MAIT cells and report virus-mediated impairment of activation, cytokine production, and altered transcription factor expression by VZV infected (antigen+) and VZV exposed (antigen-) MAIT cells in response to TCR-dependent and -independent stimulation. Furthermore, we reveal that suppression of VZV exposed (antigen-) MAIT cells is not mediated by a soluble factor from neighbouring VZV infected (antigen+) MAIT cells. Finally, we demonstrate that VZV impairs the cytolytic potential of MAIT cells in response to riboflavin synthesising bacteria. In summary, we report a virus-mediated immune-evasion strategy that disarms MAIT cell responses.
Asunto(s)
Herpesvirus Humano 3 , Células T Invariantes Asociadas a Mucosa , Humanos , Células T Invariantes Asociadas a Mucosa/inmunología , Herpesvirus Humano 3/inmunología , Activación de Linfocitos/inmunología , Citocinas/metabolismo , Citocinas/inmunología , Riboflavina/inmunología , Infección por el Virus de la Varicela-Zóster/inmunología , Infección por el Virus de la Varicela-Zóster/virología , Evasión Inmune/inmunología , Herpes Zóster/inmunología , Herpes Zóster/virologíaRESUMEN
Varicella zoster virus (VZV) reactivates from ganglionic sensory neurons to produce herpes zoster (shingles) in a unilateral dermatomal distribution, typically in the thoracic region. Reactivation not only heightens the risk of stroke and other neurological complications but also increases susceptibility to co-infections with various viral and bacterial pathogens at sites distant from the original infection. The mechanism by which VZV results in complications remote from the initial foci remains unclear. Small extracellular vesicles (sEVs) are membranous signaling structures that can deliver proteins and nucleic acids to modify the function of distal cells and tissues during normal physiological conditions. Although viruses have been documented to exploit the sEV machinery to propagate infection, the role of non-infectious sEVs released from VZV-infected neurons in viral spread and disease has not been studied. Using multi-omic approaches, we characterized the content of sEVs released from VZV-infected human sensory neurons (VZV sEVs). One viral protein was detected (immediate-early 62), as well as numerous immunosuppressive and vascular disease-associated host proteins and miRNAs that were absent in sEVs from uninfected neurons. Notably, VZV sEVs are non-infectious yet transcriptionally altered primary human cells, suppressing the antiviral type 1 interferon response and promoting neuroinvasion of a secondary pathogen in vivo. These results challenge our understanding of VZV infection, proposing that the virus may contribute to distant pathologies through non-infectious sEVs beyond the primary infection site. Furthermore, this study provides a previously undescribed immune-evasion mechanism induced by VZV that highlights the significance of non-infectious sEVs in early VZV pathogenesis. IMPORTANCE: Varicella zoster virus (VZV) is a ubiquitous human virus that predominantly spreads by direct cell-cell contact and requires efficient and immediate host immune evasion strategies to spread. The mechanisms of immune evasion prior to virion entry have not been fully elucidated and represent a critical gap in our complete understanding of VZV pathogenesis. This study describes a previously unreported antiviral evasion strategy employed by VZV through the exploitation of the infected host cell's small extracellular vesicle (sEV) machinery. These findings suggest that non-infectious VZV sEVs could travel throughout the body, affecting cells remote from the site of infection and challenging the current understanding of VZV clinical disease, which has focused on local effects and direct infection. The significance of these sEVs in early VZV pathogenesis highlights the importance of further investigating their role in viral spread and secondary disease development to reduce systemic complications following VZV infections.
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Vesículas Extracelulares , Herpesvirus Humano 3 , Herpesvirus Humano 3/inmunología , Herpesvirus Humano 3/fisiología , Vesículas Extracelulares/inmunología , Vesículas Extracelulares/metabolismo , Vesículas Extracelulares/virología , Humanos , Herpes Zóster/virología , Herpes Zóster/inmunología , Animales , MicroARNs/metabolismo , MicroARNs/genética , Células Receptoras Sensoriales/virología , Infección por el Virus de la Varicela-Zóster/inmunología , Infección por el Virus de la Varicela-Zóster/virología , Proteínas Virales/metabolismo , Activación ViralRESUMEN
Herpes zoster (HZ), also known as shingles, remains a significant global health issue and most commonly seen in elderly individuals with an early exposure history to varicella-zoster virus (VZV). Currently, the licensed vaccine Shingrix, which comprises a recombinant VZV glycoprotein E (gE) formulated with a potent adjuvant AS01B, is the most effective shingles vaccine on the market. However, undesired reactogenicity and increasing global demand causing vaccine shortage, prompting the development of novel shingles vaccines. Here, we developed novel vaccine candidates utilising multiple nanoparticle (NP) platforms to display the recombinant gE antigen, formulated in an MF59-biosimilar adjuvant. In naïve mice, all tested NP vaccines induced higher humoral and cellular immune responses than Shingrix, among which, the gEM candidate induced the highest cellular response. In live attenuated VZV (VZV LAV)-primed mouse and rhesus macaque models, the gEM candidate elicited superior cell-mediated immunity (CMI) over Shingrix. Collectively, we demonstrated that NP technology remains a suitable tool for developing shingles vaccine, and the reported gEM construct is a highly promising candidate in the next-generation shingles vaccine development.
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Vacuna contra el Herpes Zóster , Herpesvirus Humano 3 , Inmunidad Celular , Nanopartículas , Proteínas del Envoltorio Viral , Animales , Ratones , Herpesvirus Humano 3/inmunología , Proteínas del Envoltorio Viral/inmunología , Vacuna contra el Herpes Zóster/inmunología , Vacuna contra el Herpes Zóster/administración & dosificación , Macaca mulatta , Herpes Zóster/prevención & control , Herpes Zóster/inmunología , Femenino , Anticuerpos Antivirales/inmunología , Anticuerpos Antivirales/sangre , Adyuvantes Inmunológicos/administración & dosificación , Humanos , Antígenos Virales/inmunología , Inmunogenicidad Vacunal , Ratones Endogámicos BALB C , NanovacunasRESUMEN
The varicella-zoster virus (VZV) is a human neurotropic herpes virus responsible for varicella and herpes zoster (HZ). Following primary infection in childhood, VZV manifests as varicella (chickenpox) and enters a period of latency within the dorsal root ganglion. A compromised cellular immune response due to aging or immunosuppression triggers viral reactivation and the development of HZ (shingles). Patients with autoimmune diseases have a higher risk of developing HZ owing to the immunodeficiency associated with the disease itself and/or the use of immunosuppressive agents. The introduction of new immunosuppressive agents with unique mechanisms has expanded the treatment options for autoimmune diseases but has also increased the risk of HZ. Specifically, Janus kinase (JAK) inhibitors and anifrolumab have raised concerns regarding HZ. Despite treatment advances, a substantial number of patients suffer from complications such as postherpetic neuralgia for prolonged periods. The adjuvanted recombinant zoster vaccine (RZV) is considered safe and effective even in immunocompromised patients. The widespread adoption of RZV may reduce the health and socioeconomic burdens of HZ patients. This review covers the link between VZV and autoimmune diseases, assesses the risk of HZ associated with immunosuppressant use, and discusses the benefits and risks of using RZV in patients with autoimmune diseases.
Asunto(s)
Enfermedades Autoinmunes , Vacuna contra el Herpes Zóster , Herpes Zóster , Herpesvirus Humano 3 , Humanos , Herpesvirus Humano 3/inmunología , Enfermedades Autoinmunes/inmunología , Enfermedades Autoinmunes/virología , Vacuna contra el Herpes Zóster/inmunología , Vacuna contra el Herpes Zóster/uso terapéutico , Herpes Zóster/prevención & control , Herpes Zóster/inmunología , Herpes Zóster/virología , Vacunas Sintéticas/inmunología , Vacunas Sintéticas/uso terapéutico , Inmunosupresores/uso terapéutico , Neuralgia Posherpética/inmunología , Neuralgia Posherpética/prevención & controlRESUMEN
The Varicella-zoster virus (VZV), classified as a neurotropic member of the Herpesviridae family, exhibits a characteristic pathogenicity, predominantly inducing varicella, commonly known as chickenpox, during the initial infectious phase, and triggering the reactivation of herpes zoster, more commonly recognized as shingles, following its emergence from a latent state. The pathogenesis of VZV-associated neuroinflammation involves a complex interplay between viral replication within sensory ganglia and immune-mediated responses that contribute to tissue damage and dysfunction. Upon primary infection, VZV gains access to sensory ganglia, establishing latent infection within neurons. During reactivation, the virus can spread along sensory nerves, triggering a cascade of inflammatory mediators, chemokines, and immune cell infiltration in the affected neural tissues. The role of both adaptive and innate immune reactions, including the contributions of T and B cells, macrophages, and dendritic cells, in orchestrating the immune-mediated damage in the central nervous system is elucidated. Furthermore, the aberrant activation of the natural defence mechanism, characterised by the dysregulated production of immunomodulatory proteins and chemokines, has been implicated in the pathogenesis of VZV-induced neurological disorders, such as encephalitis, myelitis, and vasculopathy. The intricate balance between protective and detrimental immune responses in the context of VZV infection emphasises the necessity for an exhaustive comprehension of the immunopathogenic mechanisms propelling neuroinflammatory processes. Despite the availability of vaccines and antiviral therapies, VZV-related neurological complications remain a significant concern, particularly in immunocompromised individuals and the elderly. Elucidating these mechanisms might facilitate the emergence of innovative immunomodulatory strategies and targeted therapies aimed at mitigating VZV-induced neuroinflammatory damage and improving clinical outcomes. This comprehensive understanding enhances our grasp of viral pathogenesis and holds promise for pioneering therapeutic strategies designed to mitigate the neurological ramifications of VZV infections.
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Herpesvirus Humano 3 , Humanos , Herpesvirus Humano 3/inmunología , Herpesvirus Humano 3/fisiología , Herpesvirus Humano 3/patogenicidad , Herpes Zóster/virología , Herpes Zóster/inmunología , Infección por el Virus de la Varicela-Zóster/inmunología , Infección por el Virus de la Varicela-Zóster/virología , Enfermedades del Sistema Nervioso/virología , Enfermedades del Sistema Nervioso/inmunología , Enfermedades del Sistema Nervioso/etiología , Animales , Varicela/virología , Varicela/inmunología , Enfermedades Neuroinflamatorias/inmunología , Enfermedades Neuroinflamatorias/virologíaAsunto(s)
Vacuna contra el Herpes Zóster , Herpes Zóster , Lupus Eritematoso Sistémico , Humanos , Herpes Zóster/prevención & control , Herpes Zóster/inmunología , Herpes Zóster/epidemiología , Vacuna contra el Herpes Zóster/administración & dosificación , Vacuna contra el Herpes Zóster/uso terapéutico , Lupus Eritematoso Sistémico/inmunología , Consejo , VacunaciónRESUMEN
BACKGROUND: The adjuvanted herpes zoster subunit vaccine has shown good efficacy and safety in the general population. However, its effectiveness has not been comprehensively assessed in patients with systemic lupus erythematosus (SLE). This study aimed to evaluate the immunogenicity and safety of the adjuvanted herpes zoster subunit vaccine in patients with SLE. METHODS: This single-centre, randomised, double-blind, placebo-controlled, trial was done at the rheumatology outpatient clinic at Seoul National University Hospital, South Korea. Patients (aged ≥19 years) with clinically stable SLE and previous exposure (≥4 weeks) to immunosuppressive drugs were randomly assigned (4:1) via a central interactive web response system to receive herpes zoster subunit vaccine or placebo (0·5 mL intramuscular injection) at weeks 0 and 8. Investigators and participants were masked to intervention and group assignment. Anti-glycoprotein E antibody titres and glycoprotein E-specific cell-mediated vaccine responses were evaluated at baseline and at week 8 after the first dose, and at week 4, week 26, and week 52 after the second dose using enzyme-linked immunosorbent assay and flow cytometry, respectively. Reactogenicity, SLE disease activity, including Systemic Lupus Erythematosus Disease Activity Index 2000 and British Isles Lupus Assessment Group-flare rate, were examined. The primary outcome was the proportion of patients with a positive humoral vaccine response 4 weeks after the second dose. The primary and safety analyses were done in a modified intention-to-treat population. This study is registered with ClinicalTrials.gov, NCT06001606. FINDINGS: Between June 14, and July 19, 2023, 65 patients with SLE were enrolled, of whom 52 were randomly assigned to the herpes zoster subunit vaccine and 13 to placebo. 49 patients in the vaccine group and 11 patients in the placebo group were included in the modified intention-to-treat population. 56 (93%) of 60 patients were women and four (7%) were men. Mean age was 48·7 years (SD 11·4). The proportion of participants with a humoral vaccine response at 4 weeks after the second dose was significantly higher in the vaccine group (48 [98%] of 49 participants) than the placebo group (none [0%] of 11 patients; p<0·0001). More patients in the vaccine group than placebo group reported injection site reactions (42 patients vs two patients), fever (ten vs none), and fatigue (26 vs two). There were no differences in Systemic Lupus Erythematosus Disease Activity Index 2000 and British Isles Lupus Assessment Group-flare rates between the groups. There were no treatment-related deaths. INTERPRETATION: The herpes zoster subunit vaccine induces humoral and cellular immunity against herpes zoster with a good safety profile in patients with SLE. A larger study is warranted to assess the efficacy of vaccines to prevent herpes zoster in patients with SLE. FUNDING: Ministry of Science and ICT, The Government of the Republic of Korea.
Asunto(s)
Vacuna contra el Herpes Zóster , Lupus Eritematoso Sistémico , Vacunas de Subunidad , Humanos , Lupus Eritematoso Sistémico/inmunología , Femenino , Método Doble Ciego , Masculino , Vacuna contra el Herpes Zóster/inmunología , Vacuna contra el Herpes Zóster/administración & dosificación , Vacuna contra el Herpes Zóster/efectos adversos , República de Corea/epidemiología , Adulto , Persona de Mediana Edad , Vacunas de Subunidad/inmunología , Vacunas de Subunidad/administración & dosificación , Vacunas de Subunidad/efectos adversos , Vacunas de Subunidad/uso terapéutico , Herpes Zóster/prevención & control , Herpes Zóster/inmunología , Adyuvantes Inmunológicos/administración & dosificación , Adyuvantes Inmunológicos/efectos adversos , Inmunogenicidad Vacunal , Anticuerpos Antivirales/sangreRESUMEN
Varicella-zoster virus (VZV), a common pathogen with humans as the sole host, causes primary infection and undergoes a latent period in sensory ganglia. The recurrence of VZV is often accompanied by severe neuralgia in skin tissue, which has a serious impact on the life of patients. During the acute infection of VZV, there are few related studies on the pathophysiological mechanism of skin tissue. In this study, transcriptome sequencing data from the acute response period within 2 days of VZV antigen stimulation of the skin were used to explore a model of the trajectory of skin tissue changes during VZV infection. It was found that early VZV antigen stimulation caused activation of mainly natural immune-related signaling pathways, while in the late phase activation of mainly active immune-related signaling pathways. JAK-STAT, NFκB, and TNFα signaling pathways are gradually activated with the progression of infection, while Hypoxia is progressively inhibited. In addition, we found that dendritic cell-mediated immune responses play a dominant role in the lesion damage caused by VZV antigen stimulation of the skin. This study provides a theoretical basis for the study of the molecular mechanisms of skin lesions during acute VZV infection.
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Herpesvirus Humano 3 , Transducción de Señal , Piel , Infección por el Virus de la Varicela-Zóster , Herpesvirus Humano 3/genética , Piel/patología , Piel/virología , Piel/inmunología , Animales , Infección por el Virus de la Varicela-Zóster/virología , Infección por el Virus de la Varicela-Zóster/inmunología , Infección por el Virus de la Varicela-Zóster/genética , Infección por el Virus de la Varicela-Zóster/patología , Humanos , Ratones , Células Dendríticas/inmunología , Herpes Zóster/virología , Herpes Zóster/patología , Herpes Zóster/genética , Herpes Zóster/inmunología , Transcriptoma , Modelos Animales de Enfermedad , Antígenos Virales/inmunología , Antígenos Virales/genética , FN-kappa B/metabolismo , FN-kappa B/genéticaRESUMEN
Few papers focus their attention on VZV vaccination effectiveness among people living with HIV (PLWH). Flanking the live attenuated vaccine (VZL) available, a newly recombinant vaccine (RZV) was recently introduced and approved for HZ prevention among adults. PLWH represents a population on which a particular attention should be applied, in order to guarantee the vaccine efficacy and safety. We performed a literature search in USNLM, PubMed, PubMed Central, PMC and Cochrane Library. From all the publications found eligible, data were extracted and processed per population, vaccine type, immunogenicity and ADRs. The review of the 13 included studies shows that both RZV and VZL are immunogenic and have an acceptable safety profile in adults and children living with HIV. However, given the lack of research available about vaccine efficacy in preventing VZV and HZ in PLWH, additional studies need to be performed, in order to achieve a full completeness of data.
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Infecciones por VIH , Vacuna contra el Herpes Zóster , Herpes Zóster , Vacunas Atenuadas , Vacunas Sintéticas , Humanos , Vacunas Atenuadas/inmunología , Vacunas Atenuadas/efectos adversos , Vacunas Atenuadas/administración & dosificación , Infecciones por VIH/inmunología , Infecciones por VIH/prevención & control , Vacuna contra el Herpes Zóster/inmunología , Vacuna contra el Herpes Zóster/efectos adversos , Vacuna contra el Herpes Zóster/administración & dosificación , Vacunas Sintéticas/inmunología , Vacunas Sintéticas/efectos adversos , Vacunas Sintéticas/administración & dosificación , Herpes Zóster/prevención & control , Herpes Zóster/inmunología , Vacunas de Productos Inactivados/inmunología , Vacunas de Productos Inactivados/efectos adversos , Vacunas de Productos Inactivados/administración & dosificación , Inmunogenicidad Vacunal , Eficacia de las Vacunas , Herpesvirus Humano 3/inmunología , Adulto , Niño , Vacunación , Vacuna contra la Varicela/inmunología , Vacuna contra la Varicela/administración & dosificación , Vacuna contra la Varicela/efectos adversosRESUMEN
The role of T cell receptor (TCR) diversity in infectious disease susceptibility is not well understood. We use a systems immunology approach on three cohorts of herpes zoster (HZ) patients and controls to investigate whether TCR diversity against varicella-zoster virus (VZV) influences the risk of HZ. We show that CD4+ T cell TCR diversity against VZV glycoprotein E (gE) and immediate early 63 protein (IE63) after 1-week culture is more restricted in HZ patients. Single-cell RNA and TCR sequencing of VZV-specific T cells shows that T cell activation pathways are significantly decreased after stimulation with VZV peptides in convalescent HZ patients. TCR clustering indicates that TCRs from HZ patients co-cluster more often together than TCRs from controls. Collectively, our results suggest that not only lower VZV-specific TCR diversity but also reduced functional TCR affinity for VZV-specific proteins in HZ patients leads to lower T cell activation and consequently affects the susceptibility for viral reactivation.
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Herpes Zóster , Herpesvirus Humano 3 , Activación de Linfocitos , Receptores de Antígenos de Linfocitos T , Humanos , Herpes Zóster/inmunología , Herpes Zóster/virología , Receptores de Antígenos de Linfocitos T/metabolismo , Receptores de Antígenos de Linfocitos T/inmunología , Activación de Linfocitos/inmunología , Herpesvirus Humano 3/inmunología , Femenino , Persona de Mediana Edad , Masculino , Linfocitos T CD4-Positivos/inmunología , Anciano , Adulto , Epítopos de Linfocito T/inmunologíaRESUMEN
BACKGROUND AND OBJECTIVE: Recombinant zoster vaccine (RZV) is approved in adults for the prevention of herpes zoster. The effect of RZV in moderating the severity of breakthrough cases of herpes zoster has been noted but not explicitly quantified before. In this study, a meta-analysis was undertaken to estimate differential utility losses between unvaccinated (Placebo) and vaccinated (RZV) subjects in breakthrough cases of herpes zoster from three RZV clinical trials. METHODS: Differential utility losses between the two groups were estimated in units of quality-adjusted life-years (QALYs), leveraging aggregate patient data from the ZOE-50 (NCT01165177), ZOE-70 (NCT01165229), and ZOE-HSCT (NCT01610414) clinical trials. Differential utility losses and the ratio of mean utility losses were analyzed using random-effects and fixed-effects meta-regression models. RESULTS: The mean QALY loss differences between the unvaccinated (Placebo) and vaccinated (RZV) groups were 0.008, 0.004, and 0.011 in the ZOE-50, ZOE-70, and ZOE-HSCT studies, respectively, yielding an overall estimated difference of 0.007 (95% confidence interval 0.002-0.012) QALYs. Quality-adjusted life-year loss in the vaccinated group was estimated to be 35.5% of the value in the placebo group. A sensitivity analysis estimated an overall difference of 0.005 (95% confidence interval 0.001-0.009) QALYs, corresponding to 48.6% of the QALY loss value in the placebo group. CONCLUSIONS: Recombinant zoster vaccine is effective in alleviating disease severity in breakthrough cases of herpes zoster. The results may be useful in distinguishing QALY losses between vaccinated and unvaccinated cohorts in health economics studies, particularly cost-effectiveness analyses.
Herpes zoster, also known as shingles, may cause painful rashes and persistent pain for months or even years after the initial episode. Recombinant zoster vaccine is approved for the prevention of shingles. Pivotal recombinant zoster vaccine clinical trials have reported data about the impact of shingles episodes on daily activities and overall health-related quality of life. In this work, we combined data from three recombinant zoster vaccine clinical trials and compared the loss in quality of lifemeasured in quality-adjusted life-yearsincurred by vaccinated and unvaccinated subjects who experienced a shingles episode. We found that vaccinated patients experienced lower quality-adjusted life-year losses when they developed shingles compared with unvaccinated patients. Our results may be useful in assessing quality-adjusted life-year losses between vaccinated and unvaccinated cohorts in future herpes zoster vaccination health economics analyses.
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Vacuna contra el Herpes Zóster , Herpes Zóster , Años de Vida Ajustados por Calidad de Vida , Humanos , Herpes Zóster/prevención & control , Herpes Zóster/inmunología , Vacuna contra el Herpes Zóster/administración & dosificación , Vacunación/métodos , Ensayos Clínicos como AsuntoRESUMEN
Simian varicella virus (SVV) produces peripheral inflammatory responses during varicella (primary infection) and zoster (reactivation) in rhesus macaques (RM). However, it is unclear if peripheral measures are accurate proxies for central nervous system (CNS) responses. Thus, we analyzed cytokine and Aß42/Aß40 changes in paired serum and cerebrospinal fluid (CSF) during the course of infection. During varicella and zoster, every RM had variable changes in serum and CSF cytokine and Aß42/Aß40 levels compared to pre-inoculation levels. Overall, peripheral infection appears to affect CNS cytokine and Aß42/Aß40 levels independent of serum responses, suggesting that peripheral disease may contribute to CNS disease.
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Péptidos beta-Amiloides , Citocinas , Macaca mulatta , Animales , Péptidos beta-Amiloides/líquido cefalorraquídeo , Péptidos beta-Amiloides/sangre , Citocinas/líquido cefalorraquídeo , Citocinas/sangre , Activación Viral , Fragmentos de Péptidos/líquido cefalorraquídeo , Fragmentos de Péptidos/sangre , Varicellovirus/genética , Varicellovirus/inmunología , Herpesvirus Humano 3/patogenicidad , Herpesvirus Humano 3/inmunología , Infecciones por Herpesviridae/líquido cefalorraquídeo , Infecciones por Herpesviridae/virología , Infecciones por Herpesviridae/sangre , Infecciones por Herpesviridae/inmunología , Masculino , Herpes Zóster/líquido cefalorraquídeo , Herpes Zóster/virología , Herpes Zóster/sangre , Herpes Zóster/inmunología , Enfermedades de los Monos/virología , Enfermedades de los Monos/líquido cefalorraquídeo , Enfermedades de los Monos/sangreRESUMEN
INTRODUCTION: Diverse pathogens (viral, bacterial, fungal) have been associated with Alzheimer's disease (AD) and related traits in various studies. This suggests that compromised immunity, rather than specific microbes, may play a role in AD by increasing an individual's vulnerability to various infections, which could contribute to neurodegeneration. If true, then vaccines that have heterologous effects on immunity, extending beyond protection against the targeted disease, may hold a potential for AD prevention. METHODS: We evaluated the associations of common adult infections (herpes simplex, zoster (shingles), pneumonia, and recurrent mycoses), and vaccinations against shingles and pneumonia, with the risks of AD and other dementias in a pseudorandomized sample of the Health and Retirement Study (HRS). RESULTS: Shingles, pneumonia and mycoses, diagnosed between ages 65 and 75, were all associated with significantly increased risk of AD later in life, by 16 %-42 %. Pneumococcal and shingles vaccines administered between ages 65-75 were both associated with a significantly lower risk of AD, by 15 %-21 %. These effects became less pronounced when AD was combined with other dementias. DISCUSSION: Our findings suggest that both the pneumococcal polysaccharide vaccine and the live attenuated zoster vaccine can offer significant protection against AD. It remains to be determined if non-live shingles vaccine has a similar beneficial effect on AD. This study also found significant associations of various infections with the risk of AD, but not with the risks of other dementias. This indicates that vulnerability to infections may play a more significant role in AD than in other types of dementia, which warrants further investigation.
Asunto(s)
Enfermedad de Alzheimer , Humanos , Enfermedad de Alzheimer/inmunología , Enfermedad de Alzheimer/prevención & control , Anciano , Masculino , Femenino , Herpes Zóster/prevención & control , Herpes Zóster/inmunología , Vacuna contra el Herpes Zóster/inmunología , Neumonía/prevención & control , Neumonía/inmunología , Neumonía/microbiología , Micosis/prevención & control , Micosis/inmunología , Anciano de 80 o más Años , Vacunas Neumococicas/inmunología , Factores de RiesgoRESUMEN
Objetivo: Revisar las últimas evidencias publicadas respecto a la vacuna utilizada en nuestro país frente al virus del herpes zóster, desglosadas por eficacia, eficiencia, efectividad y seguridad vacunal. Incluir las recomendaciones vacunales actuales. Diseño: Revisión secundaria. Revisión cualitativa descriptiva. Revisión con el término de búsqueda de «vacuna herpes zóster» y «vacuna recombinante adyuvada de subunidades HZ/su». Estudio observacional retrospectivo. Fuentes de datos: Embase, Medline y Google Scholar. Selección de estudios: Criterio de búsqueda con los términos «Shingrix vaccine» y «Adjuvanted Herpes Zoster Subunit Vaccine». Periodo de búsqueda 2013-2023. Se seleccionaron los estudios tipificados como ensayos clínicos o ensayos clínicos randomizados. Se evaluaron 21 estudios publicados. No hubo exclusiones. Resultados: Los estudios evaluados se mostraron coherentes y en todos ellos la eficacia en personas adultas tanto para prevenir la reactivación viral como para evitar complicaciones estuvo por encima del 80%. La efectividad vacunal con 2 dosis también se mostró estar por encima del 80%. Los estudios coste/efectividad fueron siempre favorables en personas adultas, pacientes inmunodeprimidos y personas con enfermedad crónica. La seguridad de la vacuna fue evaluada en los estudios pivotales y en los estudios poscomercialización realizados (aún escasos por el corto periodo de tiempo estudiado). El perfil de seguridad de la vacuna es muy alto, y en el caso de los efectos adversos graves su frecuencia fue similar a placebo. Conclusiones: Disponemos de una vacuna efectiva y segura frente al virus del herpes zóster, que nos permite proteger a los grupos de población más vulnerables frente al virus.(AU)
Objective: To review the latest published evidence on the vaccine used in our country against the herpes zoster virus, breaking down the results according to the efficacy, efficiency, effectiveness and safety of the vaccine. Include the current recommendations for vaccination. Design: Secondary review. Descriptive qualitative review. Review using the search term herpes zoster vaccine and Adjuvanted recombinant Herpes Zoster subunit vaccine. Retrospective observational study. Data sources: Embase, Medline and Google Scholar. Selection of studies Search criterion with the terms Shingrix vaccine and Adjuvanted Herpes Zoster Subunit Vaccine. Search period 2013-2023. Studies classified as clinical trials or randomized clinical trials were selected. 21 published studies were evaluated. There were no exclusions. Results: The evaluated studies were found to be coherent and in all of them efficacy in adult individuals in preventing viral reactivation and in preventing complications was higher than 80%. The effectiveness of the vaccine after two doses was also higher than 80%. Cost-effectiveness studies were always favourable in adults, immunodepressed patients and individuals with chronic pathology. The safety of the vaccine was evaluated in the pivotal studies and in the post-commercialization studies that were undertaken (although there were few of the latter due to the short period of time studied). The safety profile of the vaccine is very high and in the case of severe adverse effects, their frequency was similar to that of a placebo. Conclusions: We have a safe and effective vaccine against the herpes zoster virus that allows us to protect the most vulnerable population groups against this virus.(AU)
Asunto(s)
Humanos , Masculino , Femenino , Atención Primaria de Salud , Vacunación , Herpes Zóster/inmunología , Herpes Zóster/prevención & control , Herpes Zóster/mortalidad , Herpesvirus Humano 3/inmunología , España , Prevención de Enfermedades , Vacuna contra el Herpes Zóster , Salud PúblicaRESUMEN
Immunity is known to persist after vaccination for varicella zoster virus, but the duration of immunity in patients who develop herpes zoster (HZ) remains unknown. To investigate the association between a past history of HZ and its occurrence in the general population. The Shozu HZ (SHEZ) cohort study included data for 12 299 individuals aged ≥50 years with information on their HZ history. Cross-sectional and 3-year follow-up studies were carried out to analyze the associations between a history of HZ (yes <10 years, yes ≥10 years, no) and the proportion of positive varicella zoster virus skin test results (erythema diameter ≥5 mm) and the risk of HZ after adjusting for potential confounding factors including age, sex, body mass index, smoking status, sleep duration, and mental stress. The incidences of positive skin test results were 87.7% (470/536) for individuals with a history of HZ <10 years ago, 82.2% (396/482) for those with a history of HZ ≥10 years, and 80.2% (3614/4509) for those with no history of HZ. The multivariable odds ratios (95% confidence intervals) of erythema diameter ≥5 mm were 2.07 (1.57-2.73) and 1. 39 (1.08-1.80) for individuals with a history <10 years and ≥10 years ago, respectively, compared with no history. The corresponding multivariable hazard ratios of HZ were 0.54 (0.34-0.85) and 1.16 (0.83-1.61), respectively. A past history of HZ <10 years ago may reduce the occurrence of HZ.
Asunto(s)
Herpes Zóster , Herpesvirus Humano 3 , Humanos , Estudios de Cohortes , Estudios Transversales , Pueblos del Este de Asia , Herpes Zóster/epidemiología , Herpes Zóster/inmunología , Incidencia , Reinfección/epidemiología , Reinfección/inmunología , Japón/epidemiologíaAsunto(s)
Vacuna nCoV-2019 mRNA-1273/efectos adversos , COVID-19/prevención & control , Herpesvirus Humano 3/fisiología , Enfermedades Reumáticas/virología , Activación Viral/efectos de los fármacos , Vacuna nCoV-2019 mRNA-1273/inmunología , Adulto , COVID-19/inmunología , COVID-19/virología , Femenino , Herpes Zóster/inducido químicamente , Herpes Zóster/inmunología , Herpes Zóster/virología , Humanos , Agentes Inmunomoduladores/efectos adversos , Infección Latente/inducido químicamente , Infección Latente/inmunología , Infección Latente/virología , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Enfermedades Reumáticas/tratamiento farmacológico , Enfermedades Reumáticas/inmunología , SARS-CoV-2/inmunología , TaiwánRESUMEN
Monoclonal B-cell lymphocytosis (MBL) and chronic lymphocytic leukemia (CLL) are clonal B-cell disorders associated with an increased risk of infections and impaired vaccination responses. We investigated the immunogenicity of recombinant zoster vaccine (RZV) in these patients. Individuals with MBL/untreated CLL and Bruton tyrosine kinase inhibitor (BTKi)-treated CLL patients were given two doses of RZV separated by 2 months. Responses assessed at 3 and 12 months from the first dose of RZV by an anti-glycoprotein E ELISA antibody assay and by dual-color Interferon-γ and Interleukin-2FLUOROSPOT assays were compared to historic controls matched by age and sex. About 62 patients (37 MBL/untreated CLL and 25 BTKi-treated CLL) were enrolled with a median age of 68 years at vaccination. An antibody response at 3 months was seen in 45% of participants, which was significantly lower compared to historic controls (63%, p = .03). The antibody response did not significantly differ between MBL/untreated CLL and BTKi-treated CLL (51% vs. 36%, respectively, p = .23). The CD4+ T-cell response to vaccination was significantly lower in study participants compared to controls (54% vs. 96%, p < .001), mainly due to lower responses among BTKi-treated patients compared to untreated MBL/CLL (32% vs. 73%, p = .008). Overall, only 29% of participants achieved combined antibody and cellular responses to RZV. Among participants with response assessment at 12 months (n = 47), 24% had antibody titers below the response threshold. Hypogammaglobulinemia and BTKi therapy were associated with reduced T-cell responses in a univariate analysis. Strategies to improve vaccine response to RZV among MBL/CLL patients are needed.