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involvement of innate immune receptors in the resolution of acute hepatitis b in woodchucks.the antiviral property of small agonist compounds activating pattern recognition receptors (prrs), including toll-like and rig-i receptors, have been preclinically evaluated and are currently tested in clinical trials against chronic hepatitis b (chb). the involvement of other prrs in modulating hepatitis b virus infection is less known. thus, woodchucks with resolving acute hepatitis b (ahb) after infection with woodchuck hepatitis virus (whv) were characterized as animals with normal or delaye ...202134367179
analysis of codon usage of horseshoe bat hepatitis b virus and its host.in the present analysis, codon usage strategies and base distribution of horseshoe bat hepatitis b virus (hbhbv) were analyzed and compared with its host rhinolophus sinicus, as no work was yet reported. the magnitude of synonymous codon usage bias (cub) in the virus and its host was low with higher proportion of the base c. notably, 21 more frequently used codons, 19 less frequently used codons and 3 underrepresented codons (tcg, acg and gcg) were found to be similar in both virus and its host ...202134171764
glucose homeostasis is dysregulated in ducks infected with duck hepatitis b virus.the association between hepatitis b virus (hbv) infection and the development of diabetes remains controversial. this study examined the effect of hbv infection on glucose homeostasis using a duck hbv (dhbv) model.202134167117
application of the woodchuck animal model for the treatment of hepatitis b virus-induced liver cancer.this review describes woodchucks chronically infected with the woodchuck hepatitis virus (whv) as an animal model for hepatocarcinogenesis and treatment of primary liver cancer or hepatocellular carcinoma (hcc) induced by the hepatitis b virus (hbv). since laboratory animal models susceptible to hbv infection are limited, woodchucks experimentally infected with whv, a hepatitis virus closely related to hbv, are increasingly used to enhance our understanding of virus-host interactions, immune res ...202134163570
preferential selection and contribution of non-structural protein 1 (ns1) to the efficient transmission of panzootic avian influenza h5n8 virus clades 2.3.4.4a and b in chickens and ducks.highly pathogenic avian influenza virus h5n8 clade 2.3.4.4 caused outbreaks in poultry at an unprecedented global scale. the virus was spread by wild birds in asia in two waves: clade 2.3.4.4a in 2014/2015 and clade 2.3.4.4b from 2016 up to today. both clades were highly virulent in chickens, but only clade b viruses exhibited high virulence in ducks. viral factors which contribute to virulence and transmission of these panzootic h5n8 2.3.4.4 viruses are largely unknown. the ns1 protein, typical ...202134160261
direct antiviral agents in hepatitis c virus related liver disease: don't count the chickens before they're hatched.since molecules with direct-acting antiviral (daa) became available, the landscape of the treatment of hepatitis c virus (hcv) infection has completely changed. the new drugs are extremely effective in eradicating infection, and treatment is very well tolerated with a duration of 8-12 wk. this review aims to report the outstanding clinical benefits of daa and to highlight their critical disadvantages, identifying some clinically relevant hot topics. first, do the rates of virological response re ...202134135553
identification of potent epitopes on hexon capsid protein and their evaluation as vaccine candidates against infections caused by members of adenoviridae family.adenoviruses cause economically important diseases in vertebrates. effective vaccines against adenoviral diseases are currently lacking. here, we report a highly conserved epitopic region on hexon proteins of adenoviruses that generate a strong immune response when used as a virus-like-particle (vlp) vaccine, produced by inserting the epitopic region into the core protein of hepatitis b virus. for evaluation of its protective efficacy, the epitopic region from a representative adenovirus, fowl a ...202134030897
immunogenicity and safety of hepatitis b vaccination in patients with type 2 diabetes in china: an open-label randomized controlled trial.hepatitis b virus (hbv) infection remains a global public health challenge. patients with diabetes are at greater risk of hbv infection than healthy people. the immunogenicity and safety of two major hepatitis b vaccines were evaluated in chinese patients with diabetes.202133992438
a systematic study of tupaia as a model for human acute hepatitis b infection.the molecular features of hepatitis b virus (hbv) infection, eradication, and pathogenesis are poorly understood, partly due to the lack of an adequate animal model that faithfully reproduces the course of infection. although tupaia belangeri were previously recognized as hbv-susceptible animals, the course of infection in adult tupaias remains obscure. herein, we performed a longitudinal study and demonstrated that adult tupaias were efficiently infected (90% infection rate) with 108 copies of ...202133952781
infectivity of rabbit haemorrhagic disease virus excreted in rabbit faecal pellets.rabbit haemorrhagic disease (rhd) is caused by a lagovirus affecting european rabbits (oryctolagus cuniculus). viral rna is detected in tissues or faeces of convalescent rabbits, suggesting persistent infections; however, this rna has not been shown to be related to infective viruses to date. in the present work, seven laboratory rabbits were challenged with the rhdv2/b virus variant. viral rna was individually detected by duplex qpcr in faeces collected for four weeks after infection, and the i ...202133930699
imaging, pathology, and immune correlates in the woodchuck hepatic tumor model.woodchucks chronically infected with woodchuck hepatitis virus (whv), which resembles human hepatitis b virus, develop spontaneous hepatic tumors and may be an important biological and immunological model for human hcc. nonetheless, this model requires further validation to fully realize its translational potential.202133728278
a hepatitis b virus causes chronic infections in equids worldwide.preclinical testing of novel therapeutics for chronic hepatitis b (chb) requires suitable animal models. equids host homologs of hepatitis c virus (hcv). because coinfections of hepatitis b virus (hbv) and hcv occur in humans, we screened 2,917 specimens from equids from five continents for hbv. we discovered a distinct hbv species (equid hbv, eqhbv) in 3.2% of donkeys and zebras by pcr and antibodies against eqhbv in 5.4% of donkeys and zebras. molecular, histopathological, and biochemical anal ...202133723007
a longitudinal observational study in two cats naturally-infected with hepadnavirus.hepatitis b virus (hbv) is a major cause of liver disease in humans including chronic hepatitis and hepatocellular carcinoma. domestic cat hepadnavirus (dch), a novel hbv-like hepadnavirus, was identified in domestic cats in 2018. from 6.5 %-10.8 % of pet cats are viremic for dch and altered serological markers suggestive of liver damage have been identified in 50 % of dch-infected cats. dch dna has been detected in association with characteristic lesions of chronic hepatitis and with hepatocell ...202133524809
pathogenicity and transmissibility assessment of two strains of human influenza virus isolated in china in 2018.influenza season occurs every year in china, but its presentation was unusual in the period from december 2017 to early 2018. during this period, influenza activity was increasing across the country and was much greater than during the same period in previous years, with great harm to people's health.202133472481
studies on the efficacy, potential cardiotoxicity and monkey pharmacokinetics of glp-26 as a potent hepatitis b virus capsid assembly modulator.while treatment options are available for hepatitis b virus (hbv), there is currently no cure. anti-hbv nucleoside analogs and interferon-alpha 2b rarely clear hbv covalently closed circular dna (cccdna), requiring lifelong treatment. recently, we identified glp-26, a glyoxamide derivative which modulates hbv capsid assembly. the impact of glp-26 on viral replication and integrated dna was assessed in an hbv nude mouse model bearing hbv transfected ad38 xenografts. at day 45 post-infection, glp- ...202133467678
characterization and application of precore/core-related antigens in animal models of hepatitis b virus infection.the hepatitis b core-related antigen (hbcrag), a composite antigen of precore/core gene including classical hepatitis b core protein (hbc) and hbeag and, additionally, the precore-related antigen prec, retaining the n-terminal signal peptide, has emerged as a surrogate marker to monitor the intrahepatic hbv covalently closed circular dna (cccdna) and to define meaningful treatment endpoints.202133458844
hepatitis b virus particles activate b cells through the tlr2-myd88-mtor axis.host immune control plays a pivotal role in resolving primary hepatitis-b-virus (hbv) infections. the complex interaction between hbv and host immune cells, however, remains unclear. in this study, the transcriptional profiling of specimens from animals infected with woodchuck hepatitis virus (whv) indicated tlr2 mrna accumulation as most strongly impacted during whv infection resolution as compared to other mrnas. analysis of blood transcriptional modules demonstrated that monocytes and b-cells ...202133414473
molecular detection and characterisation of domestic cat hepadnavirus (dch) from blood and liver tissues of cats in malaysia.a new domestic cat hepadnavirus (dch, family hepadnaviridae) was first reported from whole blood samples of domestic cats in australia in 2018, and from cat serum samples in italy in 2019. the pathogenesis of dch is unknown, but it was reported in cats with viraemia (6.5-10.8%), chronic hepatitis (43%) and hepatocellular carcinoma (28%). recent reports suggest that dch resembles the human hepatitis b virus (hbv) and its related hepatopathies. this study aims to detect and characterize dch among ...202133407487
diversification of mammalian deltaviruses by host shifting.hepatitis delta virus (hdv) is an unusual rna agent that replicates using host machinery but exploits hepatitis b virus (hbv) to mobilize its spread within and between hosts. in doing so, hdv enhances the virulence of hbv. how this seemingly improbable hyperparasitic lifestyle emerged is unknown, but it underpins the likelihood that hdv and related deltaviruses may alter other host-virus interactions. here, we show that deltaviruses diversify by transmitting between mammalian species. among 96,6 ...202133397804
insights into the genetic diversity, recombination, and systemic infections with evidence of intracellular maturation of hepadnavirus in cats.hepatitis b virus (hbv) is a human pathogen of global concern, while a high diversity of viruses related to hbv have been discovered in other animals during the last decade. recently, the novel mammalian hepadnavirus, tentatively named domestic cat hepadnavirus (dch), was detected in an immunocompromised cat. herein, a collection of 209 cat sera and 15 hepato-diseased cats were screened for dch using pcr, resulting in 12.4% and 20% positivity in the tested sera and necropsied cats, respectively. ...202033095800
selective usage of anp32 proteins by influenza b virus polymerase: implications in determination of host range.the influenza b virus (ibv) causes seasonal influenza and has accounted for an increasing proportion of influenza outbreaks. ibv mainly causes human infections and has not been found to spread in poultry. the replication mechanism and the determinants of interspecies transmission of ibv are largely unknown. in this study, we found that the host anp32 proteins are required for the function of the ibv polymerase. human anp32a/b strongly supports ibv replication, while anp32e has a limited role. un ...202033045004
divergent influenza-like viruses of amphibians and fish support an ancient evolutionary association.influenza viruses (family orthomyxoviridae) infect a variety of vertebrates, including birds, humans, and other mammals. recent metatranscriptomic studies have uncovered divergent influenza viruses in amphibians, fish and jawless vertebrates, suggesting that these viruses may be widely distributed. we sought to identify additional vertebrate influenza-like viruses through the analysis of publicly available rna sequencing data. accordingly, by data mining, we identified the complete coding segmen ...202032962015
characterization of seasonal pharmacokinetic variability in woodchucks.the eastern woodchuck (marmota monax) is a hibernating species extensively used as an in vivo efficacy model for chronic human hepatitis b virus infection. under laboratory conditions, woodchucks develop a pseudohibernation condition; thus, the pharmacokinetics (pk) of small-molecule therapeutics may be affected by the seasonal change. the seasonal pk of four probe compounds were characterized over 12 months in seven male and nine female laboratory-maintained woodchucks. these compounds were sel ...202032892154
antiviral therapy for the sexually transmitted viruses: recent updates on vaccine development.the sexually transmitted infections (stis) caused by viruses including human t cell leukemia virus type-1 (htlv-1), human immunodeficiency virus-1 (hiv-1), human simplex virus-2 (hsv-2), hepatitis c virus (hcv), hepatitis b virus (hbv), and human papillomavirus (hpv) are major public health issues. these infections can cause cancer or result in long-term health problems. due to high prevalence of stis, a safe and effective vaccine is required to overcome these fatal viruses.202032838584
slowly folding surface extension in the prototypic avian hepatitis b virus capsid governs stability.hepatitis b virus (hbv) is an important but difficult to study human pathogen. most basics of the hepadnaviral life-cycle were unraveled using duck hbv (dhbv) as a model although dhbv has a capsid protein (cp) comprising ~260 rather than ~180 amino acids. here we present high-resolution structures of several dhbv capsid-like particles (clps) determined by electron cryo-microscopy. as for hbv, dhbv clps consist of a dimeric α-helical frame-work with protruding spikes at the dimer interface. a fun ...202032795390
animal models for the study of human hepatitis b and d virus infection: new insights and progress.hepatitis b virus (hbv) is a member of the hepadnaviridae family and infects hepatocytes, leading to liver pathology in acutely and chronically infected individuals. co-infection with hepatitis d virus (hdv), which requires the surface proteins of hbv to replicate, can exacerbate this disease progression. thus, the >250 million people living with chronic hbv infection, including 13 million co-infected with hdv, would significantly benefit from an effective and affordable curative treatment. anim ...202032758525
innovative hbv animal models based on the entry receptor ntcp.hepatitis b is a major global health problem, with an estimated 257 million chronically infected patients and almost 1 million deaths per year. the causative agent is hepatitis b virus (hbv), a small, enveloped, partially double-stranded dna virus. hbv has a strict species specificity, naturally infecting only humans and chimpanzees. sodium taurocholate co-transporting polypeptide (ntcp), a bile acid transporter expressed on hepatocytes, has been shown to be one of the key factors in hbv infecti ...202032751581
dynamics of hepatitis b virus capsid protein dimer regulate assembly through an allosteric network.while there is an effective vaccine for human hepatitis b virus (hbv), 257 million people have chronic infections for which there is no cure. the assembly process for the viral capsid is a potential therapeutic target. in order to understand the capsid assembly process, we investigated the dimeric building blocks of the capsid. to understand what blocks assembly, we took advantage of an assembly incompetent mutant dimer, cp149-y132a, located in the interdimer interface. this mutation leads to ch ...202032662972
mammalian deltavirus without hepadnavirus coinfection in the neotropical rodent proechimys semispinosus.hepatitis delta virus (hdv) is a human hepatitis-causing rna virus, unrelated to any other taxonomic group of rna viruses. its occurrence as a satellite virus of hepatitis b virus (hbv) is a singular case in animal virology for which no consensus evolutionary explanation exists. here we present a mammalian deltavirus that does not occur in humans, identified in the neotropical rodent species proechimys semispinosus the rodent deltavirus is highly distinct, showing a common ancestor with a recent ...202032651267
genomic nucleotide-based distance analysis for delimiting old world monkey derived herpes simplex virus species.herpes simplex viruses form a genus within the alphaherpesvirus subfamily, with three identified viral species isolated from old world monkeys (owm); macacine alphaherpesvirus 1 (mchv-1; herpes b), cercopithecine alphaherpesvirus 2 (sa8), and papiine alphaherpesvirus 2 (pahv-2; herpes papio). herpes b is endemic to macaques, while pahv-2 and sa8 appear endemic to baboons. all three viruses are genetically and antigenically similar, with sa8 and pahv-2 thought to be avirulent in humans, while her ...202032590937
ati-2173, a novel liver-targeted non-chain-terminating nucleotide for hepatitis b virus cure regimens.ati-2173 is a novel liver-targeted molecule designed to deliver the 5'-monophosphate of clevudine for the treatment of chronic hepatitis b infection. unlike other nucleos(t)ides, the active clevudine-5'-triphosphate is a noncompetitive, non-chain-terminating inhibitor of hepatitis b virus (hbv) polymerase that delivers prolonged reduction of viremia in both a woodchuck hbv model and in humans for up to 6 months after cessation of treatment. however, long-term clevudine treatment was found to exh ...202032540975
efficacy of an inhibitor of hepatitis b virus expression in combination with entecavir and interferon-α in woodchucks chronically infected with woodchuck hepatitis virus.rg7834 is a small-molecule inhibitor of hepatitis b virus (hbv) gene expression that significantly reduces the levels of hepatitis b surface antigen (hbsag) and hbv dna in a humanized liver hbv mouse model. in the current study, we evaluated the potency of rg7834 in the woodchuck model of chronic hbv infection, alone and in combination with entecavir (etv) and/or woodchuck interferon-α (wifn-α). rg7834 reduced woodchuck hepatitis virus (whv) surface antigen (whsag) by a mean of 2.57 log10 from b ...202032490326
antiviral properties of extracts of streptomyces sp. smu 03 isolated from the feces of elephas maximus.actinobacteria are historically and continued to be an important source for drug discovery. the annual epidemics and periodic pandemics of humans induced by influenza a virus (iav) prompted us to develop new effective antiviral drugs with different modes of action. an actinobacterium of streptomyces sp. smu 03 was identified from the feces of elephas maximus in yunnan province, china. by employing an h5n1 pseudo-typed virus drug screening system, the anti-iav effect of the dichloromethane extrac ...202032330578
genetic and molecular features for hepadnavirus and plague infections in the himalayan marmot.the himalayan marmot (marmota himalayana), a natural host and transmitter of plague, is also susceptible to the hepadnavirus infection. to reveal the genetic basis of the hepadnavirus susceptibility and the immune response to plague, we systematically characterized the features of immune genes in himalayan marmot with those of human and mouse. we found that the entire major histocompatibility complex region and the hepatitis b virus pathway genes of the himalayan marmot were conserved with those ...202032308030
quadrivalent cell culture influenza virus vaccine. comparison to egg-derived vaccine.influenza virus infections pose a serious public health problem and vaccination is the most effective public health intervention against them. the current manufacture of influenza vaccines in embryonated chicken eggs entails significant limitations. these limitations have been overcome by producing vaccines in cell culture, which allow a faster and more flexible response to potential pandemic threats. given the impact of influenza b virus on disease burden, the availability of quadrivalent vacci ...202032255723
nanoparticle uptake in a spontaneous and immunocompetent woodchuck liver cancer model.there is a tremendous focus on the application of nanomaterials for the treatment of cancer. nonprimate models are conventionally used to assess the biomedical utility of nanomaterials. however, these animals often lack an intact immunological background, and the tumors in these animals do not develop spontaneously. we introduce a preclinical woodchuck hepatitis virus-induced liver cancer model as a platform for nanoparticle (np)-based in vivo experiments. liver cancer development in these out-b ...202032255624
toll-like receptor 8 agonist gs-9688 induces sustained efficacy in the woodchuck model of chronic hepatitis b.gs-9688 (selgantolimod) is an oral selective small molecule agonist of toll-like receptor 8 (tlr8) in clinical development for the treatment of chronic hepatitis b (chb). in this study, we evaluated the antiviral efficacy of gs-9688 in woodchucks chronically infected with woodchuck hepatitis virus (whv), a hepadnavirus closely related to hepatitis b virus (hbv). whv-infected woodchucks received eight weekly oral doses of vehicle, 1 mg/kg gs-9688 or 3 mg/kg gs-9688. vehicle and 1 mg/kg gs-9688 ha ...202032246499
safety and immunogenicity of a novel quadrivalent subunit influenza vaccine in animal models.background: compared with trivalent influenza vaccines, quadrivalent influenza vaccines are expected to provide wider protection against influenza b virus infections. we developed a novel quadrivalent subunit influenza vaccine which was distinct from the influenza vaccines available on the market in production process. in this research, we evaluated the safety and immunogenicity of the quadrivalent subunit influenza vaccine in animal models.methods: in toxicity assessment, 40 sd rats were random ...202032186950
mhc-e-restricted cd8+ t cells target hepatitis b virus-infected human hepatocytes.currently 247 million people are living with chronic hepatitis b virus infection (chb), and the development of novel curative treatments is urgently needed. immunotherapy is an attractive approach to treat chb, yet therapeutic approaches to augment the endogenous hepatitis b virus (hbv)-specific t cell response in chb patients have demonstrated little success. in this study, we show that strain 68-1 rhesus macaque (rm) cmv vaccine vectors expressing hbv ags engender hbv-specific cd8+ t cells unc ...202032161099
seroprevalence of viral infections in captive rhesus and cynomolgus macaques.macaques serve as important animal models for biomedical research. viral infection of macaques can compromise animal health as well as the results of biomedical research, and infected animals constitute an occupational health risk. therefore, monitoring macaque colonies for viral infection is an important task. we used a commercial chip-based assay to analyze sera of 231 macaques for the presence of antibody responses against nine animal and human viruses. we report high seroprevalence of cytome ...201932110713
detection systems for antibody responses against herpes b virus.herpes b virus (bv) infection is highly prevalent among adult asian macaques and rarely causes severe disease in infected animals. in contrast, bv infection of humans can induce fatal encephalitis in the absence of treatment. therefore, the development of diagnostic tests for specific and sensitive detection of antibodies against bv is an important task. the cross-reactivity of antibodies against bv with related simplex viruses of other primates may afford an opportunity to obtain sensitive dete ...201732110687
kinetics of dna damage repair response accompanying initial hepadnavirus-host genomic integration in woodchuck hepatitis virus infection of hepatocyte.mechanism of initial hepatitis b virus (hbv) integrations and kinetics of dna repair immediately after infection remain essentially unknown impairing understanding of hepadnaviral oncogenesis. wcm260 hepatocytes susceptible to hbv-compatible woodchuck hepatitis virus (whv) were examined from 15 min to 72 h post-infection (p.i.). whv strongly induced reactive oxygen species (ros), transiently inducible nitric oxide (inos) and dna damage from 15 min p.i. all initial whv-host fusions had the head-t ...202032062411
bacterial, viral, and fungal infection-related risk of parkinson's disease: meta-analysis of cohort and case-control studies.recent studies showed that patients with various bacterial, viral, and fungal infections might be at increased risk of parkinson's disease (pd). however, the risk of pd in patients with each specific infection varied. this meta-analysis estimated the association between various infections and pd risk.202032017453
effects of social reorganization on cellular immunity in male cynomolgus monkeys.exposure to acute stressors has been shown to impair cellular immunity in human beings and other animal species. comparatively little is known, however, about the effects of long-term stressors on immune function and how individual behavioral characteristics may mediate differences in immune function and clinical disease susceptibility. to determine the effects of social stress on cellular immunity and reactivation of a latent herpesvirus, 20 herpes b virus-positive male cynomolgus monkeys were ...199631918506
innate and adaptive immunity associated with resolution of acute woodchuck hepatitis virus infection in adult woodchucks.viral and/or host factors that are directly responsible for the acute versus chronic outcome of hepatitis b virus (hbv) infection have not been identified yet. information on immune response during the early stages of hbv infection in humans is mainly derived from blood samples of patients with acute hepatitis b (ahb), which are usually obtained after the onset of clinical symptoms. features of intrahepatic immune response in these patients are less studied due to the difficulty of obtaining mul ...201931869393
designing a therapeutic hepatitis b vaccine to circumvent immune tolerance.an effective prophylactic hepatitis b virus (hbv) vaccine has long been available but is ineffective for chronic infection. the primary cause of chronic hepatitis b (chb) and greatest impediment for a therapeutic vaccine is the direct and indirect effects of immune tolerance to hbv antigens. the resulting defective cd4+/cd8+ t cell response, poor cytokine production, insufficient neutralizing antibody (nab) and poor response to hbsag vaccination characterize chb infection. the objective of this ...202031809638
a fosmid-based system for the generation of recombinant cercopithecine alphaherpesvirus 2 encoding reporter genes.the transmission of macacine alphaherpesvirus 1 (mchv-1) from macaques, the natural host, to humans causes encephalitis. in contrast, human infection with cercopithecine alphaherpesvirus 2 (cehv-2), a closely related alphaherpesvirus from african vervet monkeys and baboons, has not been reported and it is believed that cehv-2 is apathogenic in humans. the reasons for the differential neurovirulence of mchv-1 and cehv-2 have not been explored on a molecular level, in part due to the absence of sy ...201931694178
the genome sequence of the eastern woodchuck (marmota monax) - a preclinical animal model for chronic hepatitis b.the eastern woodchuck (marmota monax) has been extensively used in research of chronic hepatitis b and liver cancer because its infection with the woodchuck hepatitis virus closely resembles a human hepatitis b virus infection. development of novel immunotherapeutic approaches requires genetic information on immune pathway genes in this animal model. the woodchuck genome was assembled with a combination of high-coverage whole-genome shotgun sequencing of illumina paired-end, mate-pair libraries ...201931645421
a novel hepadnavirus is associated with chronic hepatitis and hepatocellular carcinoma in cats.in 2015, over 850,000 people died from chronic hepatitis and hepatocellular carcinoma (hcc) caused by hepatitis b virus (hbv). a novel hepatitis b-like virus has recently been identified in domestic cats. the pathogenic potential of domestic cat hepadnavirus (dch), for which 6.5% to 10.8% of pet cats are viremic, is unknown. we evaluated stored formalin-fixed, paraffin-embedded biopsies of diseased and normal feline liver for the presence of dch using pcr and in situ hybridization (ish). dch was ...201931640283
liver-targeted toll-like receptor 7 agonist combined with entecavir promotes a functional cure in the woodchuck model of hepatitis b virus.current therapeutics for chronic infection with hepatitis b virus (hbv) rarely induce functional cure due to the immunotolerant status of patients. small molecule agonists targeting toll-like receptor 7 (tlr7) have been shown to elicit a functional cure in animal models of hbv but sometimes with poor tolerability due to immune-related toxicities. in an effort to increase the therapeutic window of tlr7 agonists to treat chronic hepatitis b (chb), we developed an oral tlr7 agonist, apr002, designe ...201931592075
efficacy of lenvervimab, a recombinant human immunoglobulin, in treatment of chronic hepatitis b virus infection.the mechanism of action of hepatitis b immunoglobulin (hbig) for chronic hepatitis b (chb) treatment is not fully understood. a clinical trial in japan suggested that hbig therapy might benefit patients with chb.1 lenvervimab, a recombinant monoclonal hbig developed by gc pharma (yongin, south korea), has been screened from an anti-hb-enriched phage-display library cloned from hepatitis b vaccine-boosted human blood cells and was produced in chinese hamster ovary cells.2-4.201931589980
intranasal vaccination with hbs and hbc protein combined with carboxyl vinyl polymer induces strong neutralizing antibody, anti-hbs iga, and ifng response.hepatitis b virus (hbv) infection causes acute and chronic hepatitis, which is a major public health concern worldwide. immunization methods incorporating hepatitis b surface-small (hbs-s) antigen and hepatitis b core antigen (hbc) have been proposed as candidate therapeutic vaccines, but the elimination of existing hbv infection remains a challenge. to enhance the efficacy of hbs and hbc vaccination, we investigated hbs-large (hbs-l) as an immunogen, and carboxyl vinyl polymer (cvp) as an excip ...201931582218
cross-reactive and lineage-specific single domain antibodies against influenza b hemagglutinin.influenza b virus (ibv) circulates in the human population and causes considerable disease burden worldwide, each year. current ibv vaccines can struggle to mount an effective cross-reactive immune response, as strains become mismatched, due to constant antigenic changes. additional strategies which use monoclonal antibodies, with broad reactivity, are of considerable interest, both, as diagnostics and as immunotherapeutics. alternatives to conventional monoclonal antibodies, such as single doma ...201931544820
construction of complete tupaia belangeri transcriptome database by whole-genome and comprehensive rna sequencing.the northern tree shrew (tupaia belangeri) possesses high potential as an animal model of human diseases and biology, given its genetic similarity to primates. although genetic information on the tree shrew has already been published, some of the entire coding sequences (cdss) of tree shrew genes remained incomplete, and the reliability of these cdss remained difficult to determine. to improve the determination of tree shrew cdss, we performed sequencing of the whole-genome, mrna, and total rna ...201931451757
feasibility of hepatitis b vaccination by microneedle patch: cellular and humoral immunity studies in rhesus macaques.this study evaluated dissolvable microneedle patch (dmnp) delivery of hepatitis b vaccine in rhesus macaques and provides evidence that dmnp delivery elicits seroprotective anti-hbs levels comparable with human seroprotection, potentially useful for hepatitis b birth dose vaccination in resource-constrained regions.201931408163
highly diversified shrew hepatitis b viruses corroborate ancient origins and divergent infection patterns of mammalian hepadnaviruses.shrews, insectivorous small mammals, pertain to an ancient mammalian order. we screened 693 european and african shrews for hepatitis b virus (hbv) homologs to elucidate the enigmatic genealogy of hbv. shrews host hbvs at low prevalence (2.5%) across a broad geographic and host range. the phylogenetically divergent shrew hbvs comprise separate species termed crowned shrew hbv (cshbv) and musk shrew hbv (mshbv), each containing distinct genotypes. recombination events across host orders, evolutio ...201931371507
identification of hepadnavirus in the sera of cats.hepadnaviruses infect several animal species. the prototype species, human hepatitis b virus (hbv), increases the risk of liver diseases and may cause cirrhosis and hepatocellular carcinoma. recently a novel hepadnavirus, similar to hbv, has been identified through transcriptomics studies in a domestic cat with large cell lymphoma in australia. herewith, a collection of 390 feline serum samples was screened for hepadnavirus. overall, the virus was identified in 10.8% of the sera with a significa ...201931337847
passaging of an influenza a(h1n1)pdm09 virus in a difluoro sialic acid inhibitor selects for a novel, but unfit i106m neuraminidase mutant.an influenza a(h1n1)pdm09 and an influenza b virus were passaged in 3-fluoro(eq)-4-guanidino difluoro sialic acid (3feq4gu dfsa), an inhibitor of the influenza neuraminidase (na) to determine whether resistant variants could be selected. 3feq4gu dfsa is a mechanism-based inhibitor, forming a covalent link to y406 in the na active site. given its similarity to the natural substrate, sialic acid, we predicted resistant variants would be difficult to select. yields of both viruses decreased with pa ...201931233807
detection of hepatitis b virus-like nucleotide sequences in liver samples from murine rodents and asian house shrews.in recent years, hepatitis b virus (hbv) has been detected in some species of animals. in this study, we found hbv-like nucleotide sequences in murine rodents and asian house shrews (suncus murinus) collected in china. a total of 801 animals were trapped. we found that 0.48% (3/624) of the murine rodents and 1.69% (3/177) of asian house shrews were positive for hbv-like dna. detection of hbv-like dna in brown rats (rattus norvegicus), rice-field rat (rattus losea), and asian house shrews indicat ...201931216240
the tree shrew is a promising model for the study of influenza b virus infection.influenza b virus is a main causative pathogen of annual influenza epidemics, however, research on influenza b virus in general lags behind that on influenza a viruses, one of the important reasons is studies on influenza b viruses in animal models are limited. here we investigated the tree shrew as a potential model for influenza b virus studies.201931174549
immune persistence 17 to 20 years after primary vaccination with recombination hepatitis b vaccine (cho) and the effect of booster dose vaccination.to assess the immune persistence conferred by a chinese hamster ovary (cho)-derived hepatitis b vaccine (hepb) 17 to 20 years after primary immunization during early life.201931146699
mucosal immunity against neuraminidase prevents influenza b virus transmission in guinea pigs.despite efforts to control influenza virus infection and transmission, influenza viruses still cause significant morbidity and mortality in the global human population each year. most of the current vaccines target the immunodominant hemagglutinin surface glycoprotein of the virus. however, reduced severity of disease and viral shedding have also been linked to antibodies targeting the second viral surface glycoprotein, the neuraminidase. importantly, antineuraminidase immunity was shown to be r ...201931113896
structural differences between the woodchuck hepatitis virus core protein in the dimer and capsid states are consistent with entropic and conformational regulation of assembly.hepadnaviruses are hepatotropic enveloped dna viruses with an icosahedral capsid. hepatitis b virus (hbv) causes chronic infection in an estimated 240 million people; woodchuck hepatitis virus (whv), an hbv homologue, has been an important model system for drug development. the dimeric capsid protein (cp) has multiple functions during the viral life cycle and thus has become an important target for a new generation of antivirals. purified hbv and whv cp spontaneously assemble into 120-dimer caps ...201931043524
a unique b cell epitope-based particulate vaccine shows effective suppression of hepatitis b surface antigen in mice.this study aimed to develop a novel therapeutic vaccine based on a unique b cell epitope and investigate its therapeutic potential against chronic hepatitis b (chb) in animal models.202030926653
discovery of a highly divergent hepadnavirus in shrews from china.limited sampling means that relatively little is known about the diversity and evolutionary history of mammalian members of the hepadnaviridae (genus orthohepadnavirus). an important case in point are shrews, the fourth largest group of mammals, but for which there is limited knowledge on the role they play in viral evolution and emergence. here, we report the discovery of a novel shrew hepadnavirus. the newly discovered virus, denoted shrew hepatitis b virus (shbv), is divergent to be considere ...201930884426
[swine-spread severe influenza-associated pneumonia: a case report and literature review].we report and analyze the clinical data of the first case of severe pneumonia caused by influenza b virus from swine. the patient, a 62 year-old male domestic pig breeder, was admitted to hospital because of fever and muscle pain for 5 days, and anhelation for 3 days. one week before the onset of disease, the patient kept close contact with pigs. ct scan of the chest showed diffuse infiltration in both lungs. influenza b virus antigen detection (colloidal gold method) was repeatedly positive. th ...201830643075
[monoclonal antibodies to hemagglutinin of influenza b viruses victoria evolutionary lineage.]co-circulation of two evolutionary distinct lineages of influenza virus in one epidemic season has led to development specifc reagents for rapid identifcation and typing of new isolates. panel of mabs to hemagglutinin of influenza virus b/brisbane/46/15 belonging to victoria evolutionary lineage was developed. all mabs reacted in elisa with b/victoria-like strains only. there were no interactions with heterologous influenza viruses of b/yamagata lineage, seasonal and potentially pandemic influenza a ...201930641023
differential expression of woodchuck toll-like receptors 1-10 in distinct forms of infection and stages of hepatitis in experimental hepatitis b virus infection.woodchucks infected with woodchuck hepatitis virus (whv) represent a highly valuable model of human hepatitis b virus (hbv) infection, chronic hepatitis (ch), and virus induced-primary liver cancer. toll-like receptors (tlrs) are important mediators of immune responses playing pivotal roles in the pathogenesis of viral diseases; however, their expression profiles in different forms of infection and stages of hepatitis, and in healthy animals remain essentially unknown. in this study, woodchuck t ...201830581424
host biology and anthropogenic factors affect hepadnavirus infection in a neotropical bat.the tent-making bat hepatitis b virus (tbhbv) is a hepadnavirus closely related to human hepatitis b virus. the ecology of tbhbv is unclear. we show that it is widespread and highly diversified in peters' tent-making bats (uroderma bilobatum) within panama, while local prevalence varied significantly between sample sites, ranging from 0 to 14.3%. females showed significantly higher prevalence than males, and pregnant females were more often acutely infected than non-reproductive ones. the distri ...201930564998
experimental infection of racing pigeons (columba livia domestica) with highly pathogenic clade 2.3.4.4 sub-group b h5n8 avian influenza virus.reported mass mortalities in wild pigeons and doves during the 2017/2018 clade 2.3.4.4 hpai h5n8 outbreaks in south africa necessitated an investigation of healthy racing pigeons for their susceptibility and ability to transmit a clade 2.3.4.4 sub-group b virus of south african origin. pigeons challenged with medium (104.5 eid50) and high doses (106 eid50) but not a low dose (103 eid50) of virus, shed virus in low levels of <103 eid50/ml from the oropharynx and cloaca for up to eight days, with ...201830473343
woodchuck vegf (wvegf) characteristics: model for angiogenesis and human hepatocellular carcinoma directed therapies.vascular endothelial growth factor (vegf) stimulates angiogenesis. human hepatocellular carcinoma (hcc) is a vegf-driven tumor often associated with chronic hepatitis b or c virus infection. the woodchuck is a well-characterized model of hepatitis b virus related hcc and a valuable tool for translational studies of novel vegf targeted agents. we cloned the cdna encoding woodchuck vegf (wvegf), transiently expressed it in cos cells and functionally characterized the recombinant protein. the open ...201930439360
in vitro anti-hepatitis b virus activity of 2',3'-dideoxyguanosine.2',3'-dideoxyguanosine (dog) has been demonstrated to inhibit duck hepatitis b virus (dhbv) replication in vivo in a duck model of hbv infection. in the current study, the in vitro antiviral effects of dog on human and animal hepadnaviruses were investigated. our results showed that dog effectively inhibited hbv, dhbv, and woodchuck hepatitis virus (whv) replication in hepatocyte-derived cells in a dose-dependent manner, with 50% effective concentrations (ec50) of 0.3 ± 0.05, 6.82 ± 0.25, and 23 ...201830421112
hepatitis b vaccination using a dissolvable microneedle patch is immunogenic in mice and rhesus macaques.chronic hepatitis b virus infection remains a major global public health problem, accounting for about 887,000 deaths in 2015. perinatal and early childhood infections are strongly associated with developing chronic hepatitis b. adding a birth dose of the hepatitis b vaccine (hepb bd) to routine childhood vaccination can prevent over 85% of these infections. however, hepb bd coverage remains low in many global regions, with shortages of birth attendants trained to vaccinate and limited hepb bd s ...201830377659
cross-protective efficacy of monovalent live influenza b vaccines against genetically different lineages of b/victoria and b/yamagata in ferrets.currently, two genetic lineages of influenza b virus, b/victoria and b/yamagata, are cocirculating in humans in various countries. this situation has raised a question regarding the possibility of cross-protection between b components of live attenuated influenza vaccine (laiv) belonging to different lineages. this study aimed to assess in naïve ferrets the potential protective activity of monovalent b-laivs against challenge with homologous and heterologous wild-type (wt) influenza b viruses.201830246028
suitable hepatitis b vaccine for adult immunization in china: a systematic review and meta-analysis.hepatitis b virus (hbv) infection remains an important public health problem in china, and adults need to be vaccinated. this systematic review and meta-analysis assessed the appropriate immunization of adults in china. only randomized controlled trials (rcts) were eligible, and seroprotection was defined as anti-hbs≥ 10 miu/ml; 18,308 participants in 27 studies were included. relative risk (rr) and random effects models were used. twenty micrograms of hbv vaccine resulted in a better response t ...201930089437
immunogenicity of adenovirus-vector vaccine targeting hepatitis b virus: non-clinical safety assessment in non-human primates.a new promising therapeutic approach has emerged for patients chronically infected by the hepatitis b virus (hbv) with the development of a non-replicative adenovirus vector vaccine candidate (ad-hbv). the vaccine encodes a fusion protein composed of a truncated hbv core protein, mutated polymerase protein, and two envelope domains. in this study, we assessed the immunogenicity of ad-hbv administered to cynomolgus monkeys during a non-clinical safety assessment.201830041659
relationship between environmental factors and the spatial distribution of spermophilus dauricus during 2000-2015 in china.the spermophilus dauricus is a rodent species that feeds on the tender parts of plants and seeds. it is also a natural carrier of the hepatitis b virus and the main host of the plague bacillus yersinia pestis threatening human health and the cultivated ecosystems. based on ecological niche modeling (enm) for the maxent model and arcgis for the spatial analyst model, we quantified the potential risk zone and spatial pattern of the s. dauricus outbreak during 2000-2015. we analyze the temporal and ...201830019314
anti-influenza a viral butenolide from streptomyces sp. smu03 inhabiting the intestine of elephas maximus.actinobacteria are a phylum of bacteria known for their potential in producing structurally diversified natural products that are always associated with a broad range of biological activities. in this paper, using an h5n1 pseudo-typed virus drug screening system combined with a bioassay guided purification approach, an antiviral butanolide (1) was identified from the culture broth of streptomyces sp. smu03, a bacterium isolated from the feces of elephas maximus in yunnan province, china. this co ...201829976861
2,4-diaminoquinazolines as dual toll-like receptor (tlr) 7/8 modulators for the treatment of hepatitis b virus.a novel series of 2,4-diaminoquinazolines was identified as potent dual toll-like receptor (tlr) 7 and 8 agonists with reduced off-target activity. the stereochemistry of the amino alcohol was found to influence the tlr7/8 selectivity with the ( r) isomer resulting in selective tlr8 agonism. lead optimization toward a dual agonist afforded ( s)-3-((2-amino-8-fluoroquinazolin-4-yl)amino)hexanol 31 as a potent analog, being structurally different from previously described dual agonists ( mcgowan j ...201829965759
chinese woodchucks with different susceptibility to whv infection differ in their genetic background exemplified by cytochrome b and mhc-drb molecules.chinese woodchucks (m. himalayana) were recently found to be susceptible to woodchuck hepatitis virus (whv) infection. in this study, we aimed to determine the susceptibility to whv infection of m. himalayana from different areas and their association with the animal genetic background exemplified by cytochrome b and mhc-drb molecules.201829914514
characterisation of the hepatitis b virus cross-species transmission pattern via na+/taurocholate co-transporting polypeptides from 11 new world and old world primate species.the hepatic na+/taurocholate co-transporting polypeptide (ntcp in man, ntcp in animals) is the high-affinity receptor for the hepatitis b (hbv) and hepatitis d (hdv) viruses. species barriers for human hbv/hdv within the order primates were previously attributed to ntcp sequence variations that disable virus-receptor interaction. however, only a limited number of primate ntcps have been analysed so far. in the present study, a total of 11 ntcps from apes, old and new world monkeys were cloned an ...201829912972
long-term surveillance of langur alphaherpesvirus in a zoo population of silvered langurs ( trachypithecus cristatus).langur alphaherpesvirus (hvl), a provisionally named alphaherpesvirus in the simplexvirus genus, was first identified in 1991 at the bronx zoo in wild-origin silvered langurs ( trachypithecus cristatus) and their descendants. hvl is closely related to b virus ( macacine alphaherpesvirus 1) based on serologic and genetic data, but its natural history and zoonotic potential remain unknown. a cohort study was undertaken to describe the epidemiology, clinical impact, and potential management implica ...201829900798
the immune response of rhesus macaques to novel vaccines comprising hepatitis b virus s, pres1, and core antigens.therapeutic vaccines represent a unique approach to hepatitis b virus (hbv) treatment and have the potential to induce long-term control of infection. this study explored the immune responses of rhesus macaques to novel vaccines comprising the s, pres1, and core antigens of the hbv that showed promise as prophylactic and therapeutic approaches in a mouse model. the tested vaccines included two dna vaccines (pvrc-ss1, pvrc-cs1), an hbv particle subunit (hbss1) vaccine and the recombinant vaccinia ...201829778513
a novel hepadnavirus identified in an immunocompromised domestic cat in australia.high-throughput transcriptome sequencing allows for the unbiased detection of viruses in host tissues. the application of this technique to immunosuppressed animals facilitates the detection of viruses that might otherwise be excluded or contained in immunocompetent individuals. to identify potential viral pathogens infecting domestic cats we performed high-throughput transcriptome sequencing of tissues from cats infected with feline immunodeficiency virus (fiv). a novel member of the hepadnavir ...201829772771
questioning the extreme neurovirulence of monkey b virus (macacine alphaherpesvirus 1).monkey b virus (macacine alphaherpesvirus 1; bv) occurs naturally in macaques of the genus macaca, which includes rhesus and long-tailed (cynomolgus) monkeys that are widely used in biomedical research. bv is closely related to the human herpes simplex viruses (hsv), and bv infections in its natural macaque host are quite similar to hsv infections in humans. zoonotic bv is extremely rare, having been diagnosed in only a handful of north american facilities with the last documented case occurring ...201829666644
animal models for the study of hepatitis b virus infection.even with an effective vaccine, an estimated 240 million people are chronically infected with hepatitis b virus (hbv) worldwide. current antiviral therapies, including interferon and nucleot(s)ide analogues, rarely cure chronic hepatitis b. animal models are very crucial for understanding the pathogenesis of chronic hepatitis b and developing new therapeutic drugs or strategies. hbv can only infect humans and chimpanzees, with the use of chimpanzees in hbv research strongly restricted. thus, mos ...201829511142
safety and efficacy of anti-pd-l1 therapy in the woodchuck model of hbv infection.immune clearance of hepatitis b virus (hbv) is characterized by broad and robust antiviral t cell responses, while virus-specific t cells in chronic hepatitis b (chb) are rare and exhibit immune exhaustion that includes programmed-death-1 (pd-1) expression on virus-specific t cells. thus, an immunotherapy able to expand and activate virus-specific t cells may have therapeutic benefit for chb patients. like hbv-infected patients, woodchucks infected with woodchuck hepatitis virus (whv) can have i ...201829444087
tlr7 agonist increases responses of hepatitis b virus-specific t cells and natural killer cells in patients with chronic hepatitis b treated with nucleos(t)ide analogues.the oral toll-like receptor (tlr) 7 agonist gs-9620 has antiviral effects in woodchuck and chimpanzee models of chronic hepatitis b virus (hbv) infection. we investigated, in a clinical trial, the capacity of this agent to reconstitute protective immunity in patients with chronic hbv infection.201829378197
macacine herpesvirus 1 antibody prevalence and dna shedding among invasive rhesus macaques, silver springs state park, florida, usa.we compiled records on macacine herpesvirus 1 (mchv-1) seroprevalence and, during 2015-2016, collected saliva and fecal samples from the free-ranging rhesus macaques of silver springs state park, a popular public park in central florida, usa, to determine viral dna shedding and perform sequencing. phylogenetic analysis of the us5 and us5-us6 intragenic sequence from free-ranging and laboratory mchv-1 variants did not reveal genomic differences. in animals captured during 2000-2012, average annua ...201829350146
is it possible to develop cancer vaccines to neoantigens, what are the major challenges, and how can these be overcome? neoantigens: nothing new in spite of the name.the term "neoantigen," as applied to molecules newly expressed on tumor cells, has a long history. the groundbreaking discovery of a cancer causing virus in chickens by rous over 100 years ago, followed by discoveries of other tumor-causing viruses in animals, suggested a viral etiology of human cancers. the search for other oncogenic viruses in the 1960s and 1970s resulted in the discoveries of epstein-barr virus (ebv), hepatitis b virus (hbv), and human papilloma virus (hpv), and continues unt ...201729254980
toll-like receptor 7 agonist gs-9620 induces prolonged inhibition of hbv via a type i interferon-dependent mechanism.gs-9620, an oral agonist of toll-like receptor 7 (tlr7), is in clinical development for the treatment of chronic hepatitis b (chb). gs-9620 was previously shown to induce prolonged suppression of serum viral dna and antigens in the woodchuck and chimpanzee models of chb. here we investigated the molecular mechanisms that contribute to the antiviral response to gs-9620 using in vitro models of hepatitis b virus (hbv) infection.201729247725
anti-hbv response to toll-like receptor 7 agonist gs-9620 is associated with intrahepatic aggregates of t cells and b cells.gs-9620, an oral agonist of toll-like receptor 7 (tlr7), is in clinical development for the treatment of chronic hepatitis b (chb). gs-9620 was previously shown to induced prolonged suppression of serum viral dna and antigens in the chimpanzee and woodchuck models of chb. here we investigated the immunomodulatory mechanisms underlying these antiviral effects.201729247724
hepatocytic expression of human sodium-taurocholate cotransporting polypeptide enables hepatitis b virus infection of macaques.hepatitis b virus (hbv) is a major global health concern, and the development of curative therapeutics is urgently needed. such efforts are impeded by the lack of a physiologically relevant, pre-clinical animal model of hbv infection. here, we report that expression of the hbv entry receptor, human sodium-taurocholate cotransporting polypeptide (hntcp), on macaque primary hepatocytes facilitates hbv infection in vitro, where all replicative intermediates including covalently closed circular dna ...201729247188
syrian hamster as an animal model for the study of human influenza virus infection.ferrets and mice are frequently used as animal models for influenza research. however, ferrets are demanding in terms of housing space and handling, whereas mice are not naturally susceptible to infection with human influenza a or b viruses. therefore, prior adaptation of human viruses is required for their use in mice. in addition, there are no mouse-adapted variants of the recent h3n2 viruses, because these viruses do not replicate well in mice. in this study, we investigated the susceptibilit ...201729212926
new avian hepadnavirus in palaeognathous bird, germany.in 2015, we identified an avian hepatitis b virus associated with hepatitis in a group of captive elegant-crested tinamous (eudromia elegans) in germany. the full-length genome of this virus shares <76% sequence identity with other avihepadnaviruses. the virus may therefore be considered a new extant avian hepadnavirus.201729148393
immunization with live human rhinovirus (hrv) 16 induces protection in cotton rats against hrv14 infection.human rhinoviruses (hrvs) are the main cause of cold-like illnesses, and currently no vaccine or antiviral therapies against hrvs are available to prevent or mitigate hrv infection. there are more than 150 antigenically heterogeneous hrv serotypes, with ∼90 hrvs belonging to major group species a and b. development of small animal models that are susceptible to infection with major group hrvs would be beneficial for vaccine research. previously, we showed that the cotton rat (sigmodon hispidus) ...201728912760
tumour virus epidemiology.a viral etiology of cancer was first demonstrated in 1911 by peyton rous who injected cell-free filtrate from a chicken sarcoma into healthy chickens and found it induced a tumour. since the discovery over 50 years ago of the epstein-barr virus as the cause of burkitt lymphoma, seven other human viruses or groups of viruses-hepatitis b virus, hepatitis c virus, human immunodeficiency virus type 1, some human papillomaviruses, human t-cell lymphotropic virus type 1, kaposi sarcoma-associated herp ...201728893933
identification of unique b virus (macacine herpesvirus 1) epitopes of zoonotic and macaque isolates using monoclonal antibodies.our overall aim is to develop epitope-based assays for accurate differential diagnosis of b virus zoonotic infections in humans. antibodies to cross-reacting epitopes on human-simplexviruses continue to confound the interpretation of current assays where abundant antibodies exist from previous infections with hsv types 1 and 2. to find b virus-specific epitopes we cloned ten monoclonal antibodies (mabs) from the hybridomas we produced. our unique collection of rare human sera from symptomatic an ...201728783746
construction of a hepatitis b virus neutralizing chimeric monoclonal antibody recognizing escape mutants of the viral surface antigen (hbsag).hepatitis b virus (hbv) infection is a global burden on the health-care system and is considered as the tenth leading cause of death in the world. over 248 million patients are currently suffering from chronic hbv infection worldwide and annual mortality rate of this infection is 686000. the "a" determinant is a hydrophilic region present in all antigenic subtypes of hepatitis b surface antigen (hbsag), and antibodies against this region can neutralize the virus and are protective against all su ...201728641998
rationally designed influenza virus vaccines that are antigenically stable during growth in eggs.influenza virus vaccine production is currently limited by the ability to grow circulating human strains in chicken eggs or in cell culture. to facilitate cost-effective growth, vaccine strains are serially passaged under production conditions, which frequently results in mutations of the major antigenic protein, the viral hemagglutinin (ha). human vaccination with an antigenically drifted strain is known to contribute to poor vaccine efficacy. to address this problem, we developed a replication ...201728588131
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