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Human Vaccines & Immunotherapeutics Nov 2021Immunocompromised individuals, particularly autologous hematopoietic stem cell transplant (auHSCT) recipients, are at high risk for herpes zoster (HZ). We provide an... (Randomized Controlled Trial)
Randomized Controlled Trial
Immunocompromised individuals, particularly autologous hematopoietic stem cell transplant (auHSCT) recipients, are at high risk for herpes zoster (HZ). We provide an in-depth description of humoral and cell-mediated immune (CMI) responses by age (protocol-defined) or underlying disease (post-hoc) as well as efficacy by underlying disease (post-hoc) of the adjuvanted recombinant zoster vaccine (RZV) in a randomized observer-blind phase III trial (ZOE-HSCT, NCT01610414). 1846 adult auHSCT recipients were randomized to receive a first dose of either RZV or placebo 50-70 days post-auHSCT, followed by the second dose at 1-2 months (M) later. In cohorts of 114-1721 participants, at 1 M post-second vaccine dose: Anti-gE antibody geometric mean concentrations (GMCs) and median gE-specific CD4[2+] T-cell frequencies (CD4 T cells expressing ≥2 of four assessed activation markers) were similar between 18-49 and ≥50-year-olds. Despite lower anti-gE antibody GMCs in non-Hodgkin B-cell lymphoma (NHBCL) patients, CD4[2+] T-cell frequencies were similar between NHBCL and other underlying diseases. The proportion of polyfunctional CD4 T cells increased over time, accounting for 79.6% of gE-specific CD4 T cells at 24 M post-dose two. Vaccine efficacy against HZ ranged between 42.5% and 82.5% across underlying diseases and was statistically significant in NHBCL and multiple myeloma patients. In conclusion, two RZV doses administered early post-auHSCT induced robust, persistent, and polyfunctional gE-specific immune responses. Efficacy against HZ was also high in NHBCL patients despite the lower humoral response.
Topics: Hematopoietic Stem Cell Transplantation; Herpes Zoster; Herpes Zoster Vaccine; Herpesvirus 3, Human; Humans; Immunity, Cellular; Vaccine Efficacy
PubMed: 34406911
DOI: 10.1080/21645515.2021.1953346 -
PloS One 2023This study carried out a systematic literature review of economic evaluations of varicella vaccination programmes from the earliest publication to the present day,...
OBJECTIVES
This study carried out a systematic literature review of economic evaluations of varicella vaccination programmes from the earliest publication to the present day, including programmes in the workplace and in special risk groups as well as universal childhood vaccination and catch up programmes.
METHODS
Articles published from 1985 until 2022 were sourced from PubMed/Medline, Embase, Web of Science, NHSEED and Econlit. Eligible economic evaluations, which included posters and conference abstracts, were identified by two reviewers who scrutinised each other's selections at both title and abstract and full report stages. The studies are described in terms of their methodological characteristics. Their results are aggregated by type of vaccination programme and the nature of the economic outcome.
RESULTS
A total of 2575 articles were identified of which 79 qualified as economic evaluations. A total of 55 studies focused on universal childhood vaccination, 10 on the workplace and 14 on high risk groups. Twenty-seven studies reported estimates of incremental cost per quality-adjusted life year (QALY) gained, 16 reported benefit-cost ratios, 20 reported cost-effectiveness outcomes in terms of incremental cost per event or life saved and 16 reported cost-cost offset results. Most studies of universal childhood vaccination reported an increase in overall costs to health services, but often a reduction in cost from a societal perspective.
CONCLUSIONS
The evidence surrounding the cost-effectiveness of varicella vaccination programmes remains sparse with contrasting conclusions in some areas. Future research should particularly aim to encompass the impact of universal childhood vaccination programmes on herpes zoster among adults.
Topics: Adult; Humans; Chickenpox; Cost-Benefit Analysis; Herpes Zoster; Vaccination; Herpesvirus 3, Human; Quality-Adjusted Life Years
PubMed: 36972249
DOI: 10.1371/journal.pone.0282327 -
Viruses Apr 2022Suid herpesvirus 1 (SuHV-1), known as pseudorabies virus (PRV), is one of the most devastating swine pathogens in China, particularly the sudden occurrence of PRV...
Suid herpesvirus 1 (SuHV-1), known as pseudorabies virus (PRV), is one of the most devastating swine pathogens in China, particularly the sudden occurrence of PRV variants in 2011. The higher pathogenicity and cross-species transmission potential of the newly emerged variants caused not only colossal economic losses, but also threatened public health. To uncover the underlying pathogenesis of PRV variants, Tandem Mass Tag (TMT)-based proteomic analysis was performed to quantitatively screen the differentially expressed cellular proteins in PRV-infected Vero cells. A total of 7072 proteins were identified and 960 proteins were significantly regulated: specifically 89 upregulated and 871 downregulated. To make it more credible, the expression of XRCC5 and XRCC6 was verified by western blot and RT-qPCR, and the results dovetailed with the proteomic data. The differentially expressed proteins were involved in various biological processes and signaling pathways, such as chaperonin-containing T-complex, NIK/NF-κB signaling pathway, DNA damage response, and negative regulation of G2/M transition of mitotic cell cycle. Taken together, our data holistically outline the interactions between PRV and host cells, and our results may shed light on the pathogenesis of PRV variants and provide clues for pseudorabies prevention.
Topics: Animals; Chlorocebus aethiops; Herpesvirus 1, Suid; Proteomics; Pseudorabies; Signal Transduction; Swine; Swine Diseases; Vero Cells
PubMed: 35458485
DOI: 10.3390/v14040755 -
Journal of Korean Medical Science Sep 2018Varicella-zoster virus (VZV) causes a highly contagious and generally benign, self-limited disease. However, in high-risk populations including immunocompromised... (Review)
Review
Varicella-zoster virus (VZV) causes a highly contagious and generally benign, self-limited disease. However, in high-risk populations including immunocompromised patients, pregnant women, and neonates, VZV infection can be associated with significant morbidity and mortality. Healthcare-associated transmission of VZV occurs among healthcare workers (HCWs) and patients by airborne transmission or by direct contact with the index case. To minimize the risk of transmission in healthcare settings, all VZV-susceptible HCWs should be encouraged strongly to be immunized with the varicella vaccine. For post-exposure management, active immunization (varicella vaccine), passive immunization (varicella-zoster immune globulin) and/or antiviral agents, and isolation could be used in specific situations. To prevent the transmission of VZV infection in the hospital settings, the development and implementation of hospital policies for appropriate infection control is also warranted. This article reviews the general information and healthcare-associated transmission of VZV and summarizes the recommendations for the pre- and post-exposure management of HCWs and patients, in hospital settings.
Topics: Chickenpox; Chickenpox Vaccine; Female; Health Personnel; Herpes Zoster; Herpesvirus 3, Human; Hospitals; Humans; Infant, Newborn; Occupational Exposure; Pregnancy
PubMed: 30181734
DOI: 10.3346/jkms.2018.33.e252 -
Frontiers in Immunology 2024Type I interferons (IFN-I) are key immune messenger molecules that play an important role in viral defense. They act as a bridge between microbe sensing, immune function... (Review)
Review
Type I interferons (IFN-I) are key immune messenger molecules that play an important role in viral defense. They act as a bridge between microbe sensing, immune function magnitude, and adaptive immunity to fight infections, and they must therefore be tightly regulated. It has become increasingly evident that thymic irregularities and mutations in immune genes affecting thymic tolerance can lead to the production of IFN-I autoantibodies (autoAbs). Whether these biomarkers affect the immune system or tissue integrity of the host is still controversial, but new data show that IFN-I autoAbs may increase susceptibility to severe disease caused by certain viruses, including SARS-CoV-2, herpes zoster, and varicella pneumonia. In this article, we will elaborate on disorders that have been identified with IFN-I autoAbs, discuss models of how tolerance to IFN-Is is lost, and explain the consequences for the host.
Topics: Autoantibodies; Thymus Gland; Interferon Type I; Herpesvirus 3, Human
PubMed: 38455040
DOI: 10.3389/fimmu.2024.1327784 -
Virus Research Feb 2022Bovine alphaherpesviruses 1 and 5 (BoHV-1 and BoHV-5) are closely related viruses that co-circulate in South America and recombine in the field. The complete genomes of...
Bovine alphaherpesviruses 1 and 5 (BoHV-1 and BoHV-5) are closely related viruses that co-circulate in South America and recombine in the field. The complete genomes of three natural gB gene recombinant viruses between BoHV-1 and BoHV-5 were obtained by Illumina next-generation sequencing. Complete genome sequences of the three recombinant strains (RecA1, RecB2, and RecC2) have a similar size of approximately 138.3kb and a GC content of 75%. The genome structure corresponds to herpesvirus class D, with 69 open reading frames (ORFs) arranged in the same order as other bovine alphaherpesviruses related to BoHV-1. Their genomes were included in recombination network studies indicating statistically significant recombination evidence both based on the whole genome, as well as in the sub-regions. The novel recombinant region of 3074 nt of the RecB2 and RecC2 strains includes the complete genes of the myristylated tegument protein (UL11) and the glycoprotein M (UL10) and part of the helicase (UL9) gene, and it seems to have originated independently of the first recombinant event involving the gB gene. Phylogenetic analyzes performed with the amino acid sequences of UL9, UL 10, and UL11 indicated that RecB2 and RecC2 recombinants are closely related to the minor parental virus (BoHV-1.2b). On the contrary, RecA1 groups with the major parental (BoHV-5), thus confirming the absence of recombination in this region for this recombinant. One breakpoint in the second recombinant region lies in the middle of the UL9 reading frame, originating a chimeric enzyme half encoded by BoHV-5 and BoHV-1.2b parental strains. The chimeric helicases of both recombinants are identical and have 96.8 and 96.3% similarity with the BoHV-5 and BoHV-1 parents, respectively. In vitro characterization suggests that recombinants have delayed exit from the cell compared to parental strains. However, they produce the similar viral titer as their putative parents suggesting the accumulation of viral particles for the cell exit delayed on time. Despite in vitro different behavior, these natural recombinant viruses have been maintained in the bovine population for more than 30 years, indicating that recombination could be playing an important role in the biological diversity of these viral species. Our findings highlight the importance of studying whole genome diversity in the field and determining the role that homologous recombination plays in the structure of viral populations. A whole-genome recombinant characterization is a suitable tool to help understand the emergence of new viral forms with novel pathogenic features.
Topics: Animals; Cattle; Cattle Diseases; Herpesviridae Infections; Herpesvirus 1, Bovine; Open Reading Frames; Phylogeny; Sequence Analysis, DNA
PubMed: 34915090
DOI: 10.1016/j.virusres.2021.198656 -
Antimicrobial Agents and Chemotherapy Mar 2021Herpesviruses are widespread and can cause serious illness. Many currently available antiviral drugs have limited effects, result in rapid development of resistance, and...
Herpesviruses are widespread and can cause serious illness. Many currently available antiviral drugs have limited effects, result in rapid development of resistance, and often exhibit dose-dependent toxicity. Especially for human cytomegalovirus (HCMV), new well-tolerated compounds with novel mechanisms of action are urgently needed. In this study, we characterized the antiviral activity of two new diazadispiroalkane derivatives, 11826091 and 11826236. These two small molecules exhibited strong activity against low-passage-number HCMV. Pretreatment of cell-free virus with these compounds greatly reduced infection. Time-of-addition assays where 11826091 or 11826236 was added to cells before infection, before and during infection, or during or after infection demonstrated an inhibitory effect on early steps of infection. Interestingly, 11826236 had an effect by addition to cells after infection. Results from entry assays showed the major effect to be on attachment. Only 11826236 had a minimal effect on penetration comparable to heparin. Further, no effect on virus infection was found for cell lines with a defect in heparan sulfate expression or lacking all surface glycosaminoglycans, indicating that these small molecules bind to heparan sulfate on the cell surface. To test this further, we extended our analyses to pseudorabies virus (PrV), a member of the , which is known to use cell surface heparan sulfate for initial attachment via nonessential glycoprotein C (gC). While infection with PrV wild type was strongly impaired by 11826091 or 11826236, as with heparin, a mutant lacking gC was unaffected by either treatment, demonstrating that primary attachment to heparan sulfate via gC is targeted by these small molecules.
Topics: Alkanes; Animals; Antiviral Agents; Glycosaminoglycans; Heparin; Heparitin Sulfate; Herpesvirus 1, Suid; Humans; Spiro Compounds; Viral Envelope Proteins; Virus Internalization
PubMed: 33495228
DOI: 10.1128/AAC.02103-20 -
Scientific Reports Apr 2022Feline herpesvirus type 1 (FHV-1) is a common causative agent of domestic cats' rhinotracheitis in domestic cats, and it increasingly threatens wild felids worldwide....
Feline herpesvirus type 1 (FHV-1) is a common causative agent of domestic cats' rhinotracheitis in domestic cats, and it increasingly threatens wild felids worldwide. The endangered snow leopard (Panthera uncia) belongs to the family Felidae, and it is the top predator on the Tibetan Plateau. Here we report the identification and isolation of FHV-1 from three dead captive snow leopards that presented with sneezing and rhinorrhea. To explore the relationship between FHV-1 and their deaths, organs and nasal swabs were collected for histopathology, viral isolation and sequence analysis. The results revealed that all three snow leopards were infected with FHV-1. The first animal died primarily of cerebral infarction and secondary non-suppurative meningoencephalitis that was probably caused by FHV-1. The second animal died mainly of renal failure accompanied by interstitial pneumonia caused by FHV-1. The cause of death for the third animal was likely related to the concurrent reactivation of a latent FHV-1 infection. The gD and gE gene sequence alignment of the isolated FHV-1 isolate strain revealed that the virus likely originated from a domestic cat. It was found that FHV-1 infection can cause different lesions in snow leopards than in domestic cats and is associated with high risk of disease in wild felids. This suggests that there should be increased focus on protecting wild felids against FHV-1 infections originating from domestic cats.
Topics: Animals; Cats; Felidae; Herpesviridae Infections; Panthera; Varicellovirus
PubMed: 35484134
DOI: 10.1038/s41598-022-08994-4 -
Clinical Infectious Diseases : An... Nov 2021Although most cases of varicella or zoster are self-limited, patients with certain immune deficiencies may develop severe or life-threatening disease. (Review)
Review
BACKGROUND
Although most cases of varicella or zoster are self-limited, patients with certain immune deficiencies may develop severe or life-threatening disease.
METHODS
We studied a patient with varicella-zoster virus (VZV) central nervous system (CNS) vasculopathy and as part of the evaluation, tested his plasma for antibodies to cytokines. We reviewed the literature for cases of varicella or zoster associated with primary and acquired immunodeficiencies.
RESULTS
We found that a patient with VZV CNS vasculopathy had antibody that neutralized interferon (IFN)-α but not IFN-γ. The patient's plasma blocked phosphorylation in response to stimulation with IFN-α in healthy control peripheral blood mononuclear cells. In addition to acquired immunodeficiencies like human immunodeficiency virus (HIV) or autoantibodies to IFN, variants in specific genes have been associated with severe varicella and/or zoster. Although these genes encode proteins with very different activities, many affect IFN signaling pathways, either those that sense double-stranded RNA or cytoplasmic DNA that trigger IFN production, or those involved in activation of IFN stimulated genes in response to binding of IFN with its receptor.
CONCLUSIONS
Immune deficiencies highlight the critical role of IFN in control of VZV infections and suggest new approaches for treatment of VZV infection in patients with certain immune deficiencies.
Topics: Chickenpox; Herpes Zoster; Herpesvirus 3, Human; Humans; Interferon-alpha; Leukocytes, Mononuclear
PubMed: 32856043
DOI: 10.1093/cid/ciaa1274 -
Cleveland Clinic Journal of Medicine Sep 2021
Topics: Abdominal Muscles; Herpes Zoster; Herpesvirus 3, Human; Humans
PubMed: 34470749
DOI: 10.3949/ccjm.88a.20178