| cross-protection against h7n9 influenza strains using a live-attenuated h7n3 virus vaccine. | in 2013, avian h7n9 influenza viruses were detected infecting people in china resulting in high mortality. influenza h7 vaccines that provide cross-protection against these new viruses are needed until specific h7n9 vaccines are ready to market. in this study, an available h7n3 cold-adapted, temperature sensitive, live attenuated influenza vaccine (laiv) elicited protective immune responses in ferrets against h7n9 viruses. the h7n3 laiv administered alone (by intranasal or subcutaneous administr ... | 2015 | 25448100 |
| pathogenesis, transmissibility, and ocular tropism of a highly pathogenic avian influenza a (h7n3) virus associated with human conjunctivitis. | h7 subtype influenza a viruses, responsible for numerous outbreaks in land-based poultry in europe and the americas, have caused over 100 cases of confirmed or presumed human infection over the last decade. the emergence of a highly pathogenic avian influenza h7n3 virus in poultry throughout the state of jalisco, mexico, resulting in two cases of human infection, prompted us to examine the virulence of this virus (a/mexico/indre7218/2012 [mx/7218]) and related avian h7 subtype viruses in mouse a ... | 2013 | 23487452 |
| avian influenza h7n9/13 and h7n7/13: a comparative virulence study in chickens, pigeons, and ferrets. | human influenza cases caused by a novel avian h7n9 virus in china emphasize the zoonotic potential of that subtype. we compared the infectivity and pathogenicity of the novel h7n9 virus with those of a recent european avian h7n7 strain in chickens, pigeons, and ferrets. neither virus induced signs of disease despite substantial replication in inoculated chickens and rapid transmission to contact chickens. evidence of the replication of both viruses in pigeons, albeit at lower levels of rna excre ... | 2014 | 24899194 |
| development of a high-yield live attenuated h7n9 influenza virus vaccine that provides protection against homologous and heterologous h7 wild-type viruses in ferrets. | live attenuated h7n9 influenza vaccine viruses that possess the hemagglutinin (ha) and neuraminidase (na) gene segments from the newly emerged wild-type (wt) a/anhui/1/2013 (h7n9) and six internal protein gene segments from the cold-adapted influenza virus a/ann arbor/6/60 (aa ca) were generated by reverse genetics. the reassortant virus containing the original wt a/anhui/1/2013 ha and na sequences replicated poorly in eggs. multiple variants with amino acid substitutions in the ha head domain t ... | 2014 | 24719414 |
| pathogenesis and transmission assessments of two h7n8 influenza a viruses recently isolated from turkey farms in indiana using mouse and ferret models. | avian influenza a h7 viruses have caused multiple outbreaks in domestic poultry throughout north america, resulting in occasional infections of humans in close contact with affected birds. in early 2016, the presence of h7n8 highly pathogenic avian influenza (hpai) viruses and closely related h7n8 low-pathogenic avian influenza (lpai) viruses was confirmed in commercial turkey farms in indiana. these h7n8 viruses represent the first isolation of this subtype in domestic poultry in north america, ... | 2016 | 27681133 |
| plant-derived h7 vlp vaccine elicits protective immune response against h7n9 influenza virus in mice and ferrets. | in march 2013, the chinese centre for disease control and prevention confirmed the first reported case of human infection with an avian influenza a h7n9 virus. infection with this virus often caused severe pneumonia and acute respiratory distress syndrome resulting in a case fatality rate >35%. the risk of pandemic highlighted, once again, the need for a more rapid and scalable vaccine response capability. here, we describe the rapid (19 days) development of a plant-derived vlp vaccine based on ... | 2015 | 26432915 |
| recombinant h7 hemagglutinin forms subviral particles that protect mice and ferrets from challenge with h7n9 influenza virus. | a novel avian-origin influenza a h7n9 virus emerged in china in 2013 and continues to cause sporadic human infections with mortality rates approaching 35%. currently there are no approved human vaccines for h7n9 virus. recombinant approaches including hemagglutinin (ha) and virus-like particles (vlps) have resulted in experimental vaccines with advantageous safety and manufacturing characteristics. while high immunogenicity of vlp vaccines has been attributed to the native conformation of ha arr ... | 2015 | 26207590 |
| development of influenza a(h7n9) candidate vaccine viruses with improved hemagglutinin antigen yield in eggs. | the emergence of avian influenza a(h7n9) virus in poultry causing zoonotic human infections was reported on march 31, 2013. development of a(h7n9) candidate vaccine viruses (cvv) for pandemic preparedness purposes was initiated without delay. candidate vaccine viruses were derived by reverse genetics using the internal genes of a/puerto/rico/8/34 (pr8). the resulting a(h7n9) cvvs needed improvement because they had titers and antigen yields that were suboptimal for vaccine manufacturing in eggs, ... | 2015 | 25962412 |
| mammalian adaptation of influenza a(h7n9) virus is limited by a narrow genetic bottleneck. | human infection with avian influenza a(h7n9) virus is associated mainly with the exposure to infected poultry. the factors that allow interspecies transmission but limit human-to-human transmission are unknown. here we show that a/anhui/1/2013(h7n9) influenza virus infection of chickens (natural hosts) is asymptomatic and that it generates a high genetic diversity. in contrast, diversity is tightly restricted in infected ferrets, limiting further adaptation to a fully transmissible form. airborn ... | 2015 | 25850788 |
| evaluation of mdck cell-derived influenza h7n9 vaccine candidates in ferrets. | avian-origin influenza a (h7n9) viruses emerged as human pathogens in china in early 2013 and have killed >100 persons. influenza vaccines are mainly manufactured using egg-based technology which could not meet the surging demand during influenza pandemics. in this study, we evaluated cell-based influenza h7n9 vaccines in ferrets. an egg-derived influenza h7n9 reassortant vaccine virus was adapted in mdck cells. influenza h7n9 whole virus vaccine antigen was manufactured using a microcarrier-bas ... | 2015 | 25799397 |
| recombinant virus-like particles elicit protective immunity against avian influenza a(h7n9) virus infection in ferrets. | in march 2013, diagnosis of the first reported case of human infection with a novel avian-origin influenza a(h7n9) virus occurred in eastern china. most human cases have resulted in severe respiratory illness and, in some instances, death. currently there are no licensed vaccines against h7n9 virus, which continues to cause sporadic human infections. recombinant virus-like particles (vlps) have been previously shown to be safe and effective vaccines for influenza. in this study, we evaluated the ... | 2015 | 25772674 |
| neuraminidase mutations conferring resistance to oseltamivir in influenza a(h7n9) viruses. | human infections by avian influenza a(h7n9) virus entail substantial morbidity and mortality. treatment of infected patients with the neuraminidase (na) inhibitor oseltamivir was associated with emergence of viruses carrying na substitutions. in the na inhibition (ni) assay, r292k conferred highly reduced inhibition by oseltamivir, while e119v and i222k each caused reduced inhibition. to facilitate establishment of laboratory correlates of clinically relevant resistance, experiments were conduct ... | 2015 | 25740997 |
| impact of adjuvants on the immunogenicity and efficacy of split-virion h7n9 vaccine in ferrets. | an effective vaccine is urgently needed against the h7n9 avian influenza virus. we evaluated the immunogenicity and protective efficacy of a split-virion h7n9 vaccine with or without the oil-in-water adjuvants in ferrets. | 2015 | 25712975 |
| h7n9: preparing for the unexpected in influenza. | in the years prior to 2013, avian influenza a h7 viruses were a cause of significant poultry mortality; however, human illness was generally mild. in march 2013, a novel influenza a(h7n9) virus emerged in china as an unexpected cause of severe human illness with 36% mortality. chinese and other public health officials responded quickly, characterizing the virus and identifying more than 400 cases through use of new technologies and surveillance tools made possible by past preparedness and respon ... | 2015 | 25386931 |
| transmission of h7n9 influenza virus in mice by different infective routes. | on 19 february 2013, the first patient infected with a novel influenza a h7n9 virus from an avian source showed symptoms of sickness. more than 349 laboratory-confirmed cases and 109 deaths have been reported in mainland china since then. laboratory-confirmed, human-to-human h7n9 virus transmission has not been documented between individuals having close contact; however, this transmission route could not be excluded for three families. to control the spread of the avian influenza h7n9 virus, we ... | 2014 | 25367670 |
| a single immunization with modified vaccinia virus ankara-based influenza virus h7 vaccine affords protection in the influenza a(h7n9) pneumonia ferret model. | since the first reports in early 2013, >440 human cases of infection with avian influenza a(h7n9) have been reported including 122 fatalities. after the isolation of the first a(h7n9) viruses, the nucleotide sequences became publically available. based on the coding sequence of the influenza virus a/shanghai/2/2013 hemagglutinin gene, a codon-optimized gene was synthesized and cloned into a recombinant modified vaccinia virus ankara (mva). this mva-h7-sh2 viral vector was used to immunize ferret ... | 2015 | 25246535 |
| characterization of drug-resistant influenza a(h7n9) variants isolated from an oseltamivir-treated patient in taiwan. | patients contracting influenza a(h7n9) infection often developed severe disease causing respiratory failure. neuraminidase (na) inhibitors (nais) are the primary option for treatment, but information on drug-resistance markers for influenza a(h7n9) is limited. | 2015 | 25124927 |
| the r292k mutation that confers resistance to neuraminidase inhibitors leads to competitive fitness loss of a/shanghai/1/2013 (h7n9) influenza virus in ferrets. | neuraminidase (na) inhibitors are the only licensed therapeutic option for human zoonotic h7n9 infections. an na-r292k mutation that confers broad-spectrum resistance to na inhibitors has been documented in h7n9 patients after treatment. | 2014 | 24951824 |
| response of mice and ferrets to a monovalent influenza a (h7n9) split vaccine. | in early spring 2013, the emergence of the influenza a (h7n9) virus in humans in eastern china raised concerns of a new influenza pandemic. development of a safe and effective h7n9 influenza vaccine is urgently needed. to this end, we first synthesized the hemagglutinin (ha) and neuraminidase (na) genes of the influenza a (h7n9) virus a/anhui/1/2013. using reverse genetics, we rescued a reassortant virus (h7n9/pr8) that contained the ha and na genes from wild-type h7n9 and six genes encoding int ... | 2014 | 24937303 |
| transmissibility of novel h7n9 and h9n2 avian influenza viruses between chickens and ferrets. | previous studies have shown that the h7n9 avian influenza virus cannot be transmitted efficiently between ferrets via respiratory droplets. here, we studied the infectivity of the h7n9 avian influenza virus in chickens and its transmissibility from infected to naïve chickens and ferrets. the h7n9 virus (a/anhui/1/2013) replicated poorly in chickens and could not be transmitted efficiently from infected chickens to naïve chickens and ferrets. h7n9 virus was shed from chicken tracheae for only 2 d ... | 2014 | 24503095 |
| the mouse and ferret models for studying the novel avian-origin human influenza a (h7n9) virus. | the current study was conducted to establish animal models (including mouse and ferret) for the novel avian-origin h7n9 influenza virus. | 2013 | 23927489 |
| low pathogenic avian influenza a(h7n9) virus causes high mortality in ferrets upon intratracheal challenge: a model to study intervention strategies. | infections with low pathogenic avian influenza (lpai) a(h7n9) viruses have caused more than 100 hospitalized human cases of severe influenza in china since february 2013 with a case fatality rate exceeding 25%. most of these human infections presented with severe viral pneumonia, while limited information is available currently on the occurrence of mild and subclinical cases. in the present study, a ferret model for this virus infection in humans is presented to evaluate the pathogenesis of the ... | 2013 | 23816392 |
| the comparison of pathology in ferrets infected by h9n2 avian influenza viruses with different genomic features. | h9n2 avian influenza virus circulates widely in poultry and has been responsible for sporadic human infections in several regions. few studies have been conducted on the pathogenicity of h9n2 aiv isolates that have different genomic features. we compared the pathology induced by a novel reassortant h9n2 virus and two currently circulating h9n2 viruses that have different genomic features in ferrets. the results showed that the three viruses can induce infections with various amounts of viral she ... | 2016 | 26638019 |
| adaptation of h9n2 aiv in guinea pigs enables efficient transmission by direct contact and inefficient transmission by respiratory droplets. | h9n2 avian influenza viruses circulate worldwide in poultry and have sporadically infected humans, raising concern whether h9n2 viruses have pandemic potential. here, we use a guinea pig model to examine whether serial passage results in adaptive viral changes that confer a transmissible phenotype to a wild-type h9n2 virus. after nine serial passages of an h9n2 virus through guinea pigs, productive transmission by direct contact occurred in 2/3 guinea pig pairs. the efficiency of transmission by ... | 2015 | 26552719 |
| characterization of an h9n2 avian influenza virus from a fringilla montifringilla brambling in northern china. | avian h9n2 influenza viruses circulating in domestic poultry populations are occasionally transmitted to humans. we report the genomic characterization of an h9n2 avian influenza virus (a/brambling/beijing/16/2012) first isolated from a healthy fringilla montifringilla brambling in northern china in 2012. phylogenetic analyses revealed that this h9n2 virus belongs to the bj/94-like sublineage. this virus had a low pathogenicity for chickens and was able to replicate at a low level in mouse lung ... | 2015 | 25569456 |
| genetics, receptor binding property, and transmissibility in mammals of naturally isolated h9n2 avian influenza viruses. | h9n2 subtype influenza viruses have been detected in different species of wild birds and domestic poultry in many countries for several decades. because these viruses are of low pathogenicity in poultry, their eradication is not a priority for animal disease control in many countries, which has allowed them to continue to evolve and spread. here, we characterized the genetic variation, receptor-binding specificity, replication capability, and transmission in mammals of a series of h9n2 influenza ... | 2014 | 25411973 |
| quantitative characterization of glycan-receptor binding of h9n2 influenza a virus hemagglutinin. | avian influenza subtypes such as h5, h7 and h9 are yet to adapt to the human host so as to establish airborne transmission between humans. however, lab-generated reassorted viruses possessing hemagglutinin (ha) and neuraminidase (na) genes from an avian h9 isolate and other genes from a human-adapted (h3 or h1) subtype acquired two amino acid changes in ha and a single amino acid change in na that confer respiratory droplet transmission in ferrets. we previously demonstrated for human-adapted h1 ... | 2013 | 23626667 |
| metagenomic analysis of the ferret fecal viral flora. | ferrets are widely used as a small animal model for a number of viral infections, including influenza a virus and sars coronavirus. to further analyze the microbiological status of ferrets, their fecal viral flora was studied using a metagenomics approach. novel viruses from the families picorna-, papilloma-, and anelloviridae as well as known viruses from the families astro-, corona-, parvo-, and hepeviridae were identified in different ferret cohorts. ferret kobu- and hepatitis e virus were ma ... | 2013 | 23977082 |
| generation of influenza a viruses as live but replication-incompetent virus vaccines. | the conversion of life-threatening viruses into live but avirulent vaccines represents a revolution in vaccinology. in a proof-of-principle study, we expanded the genetic code of the genome of influenza a virus via a transgenic cell line containing orthogonal translation machinery. this generated premature termination codon (ptc)-harboring viruses that exerted full infectivity but were replication-incompetent in conventional cells. genome-wide optimization of the sites for incorporation of multi ... | 2016 | 27934767 |
| antiviral efficacy of verdinexor in vivo in two animal models of influenza a virus infection. | influenza a virus (iav) causes seasonal epidemics of respiratory illness that can cause mild to severe illness and potentially death. antiviral drugs are an important countermeasure against iav; however, drug resistance has developed, thus new therapeutic approaches are being sought. previously, we demonstrated the antiviral activity of a novel nuclear export inhibitor drug, verdinexor, to reduce influenza replication in vitro and pulmonary virus burden in mice. in this study, in vivo efficacy o ... | 2016 | 27893810 |
| antigenic characterization of h3 subtypes of avian influenza a viruses from north america. | besides humans, h3 subtypes of influenza a viruses (iavs) can infect various animal hosts, including avian, swine, equine, canine, and sea mammal species. these h3 viruses are both antigenically and genetically diverse. here, we characterized the antigenic diversity of contemporary h3 avian iavs recovered from migratory birds in north america. hemagglutination inhibition (hi) assays were performed on 37 h3 isolates of avian iavs recovered from 2007 to 2011 using generated reference chicken sera. ... | 2016 | 27309078 |
| neutralizing inhibitors in the airways of naïve ferrets do not play a major role in modulating the virulence of h3 subtype influenza a viruses. | many insights regarding the pathogenesis of human influenza a virus (iav) infections have come from studies in mice and ferrets. surfactant protein (sp)-d is the major neutralizing inhibitor of iav in mouse airway fluids and sp-d-resistant iav mutants show enhanced virus replication and virulence in mice. herein, we demonstrate that sialylated glycoproteins, rather than sp-d, represent the major neutralizing inhibitors against h3 subtype viruses in airway fluids from naïve ferrets. moreover, whi ... | 2016 | 27110707 |
| influenza a virus transmission via respiratory aerosols or droplets as it relates to pandemic potential. | many respiratory viruses of humans originate from animals. for instance, there are now eight paramyxoviruses, four coronaviruses and four orthomxoviruses that cause recurrent epidemics in humans but were once confined to other hosts. in the last decade, several members of the same virus families have jumped the species barrier from animals to humans. fortunately, these viruses have not become established in humans, because they lacked the ability of sustained transmission between humans. however ... | 2016 | 26385895 |
| modeling human influenza infection in the laboratory. | influenza is the leading cause of death from an infectious cause. because of its clinical importance, many investigators use animal models to understand the biologic mechanisms of influenza a virus replication, the immune response to the virus, and the efficacy of novel therapies. this review will focus on the biosafety, biosecurity, and ethical concerns that must be considered in pursuing influenza research, in addition to focusing on the two animal models - mice and ferrets - most frequently u ... | 2015 | 26357484 |
| synthetic long peptide influenza vaccine containing conserved t and b cell epitopes reduces viral load in lungs of mice and ferrets. | currently licensed influenza vaccines mainly induce antibodies against highly variable epitopes. due to antigenic drift, protection is subtype or strain-specific and regular vaccine updates are required. in case of antigenic shifts, which have caused several pandemics in the past, completely new vaccines need to be developed. we set out to develop a vaccine that provides protection against a broad range of influenza viruses. therefore, highly conserved parts of the influenza a virus (iav) were s ... | 2015 | 26046664 |
| ferrets exclusively synthesize neu5ac and express naturally humanized influenza a virus receptors. | mammals express the sialic acids n-acetylneuraminic acid (neu5ac) and n-glycolylneuraminic acid (neu5gc) on cell surfaces, where they act as receptors for pathogens, including influenza a virus (iav). neu5gc is synthesized from neu5ac by the enzyme cytidine monophosphate-n-acetylneuraminic acid hydroxylase (cmah). in humans, this enzyme is inactive and only neu5ac is produced. ferrets are susceptible to human-adapted iav strains and have been the dominant animal model for iav studies. here we sh ... | 2014 | 25517696 |
| enhancement of influenza virus transmission by gene reassortment. | influenza a virus is characterized by a genome composed of eight single-stranded, negative sense rna segments, which allow for reassortment between different strains when they co-infect the same host cell. reassortment is an important driving force for the evolution of influenza viruses. the ability of reassortment allows influenza virus to endlessly reinvent itself and pose a constant threat to the health of humans and other animals. of the four human influenza pandemics since the beginning of ... | 2014 | 25048543 |
| substitutions t200a and e227a in the hemagglutinin of pandemic 2009 influenza a virus increase lethality but decrease transmission. | we report that swine influenza virus-like substitutions t200a and e227a in the hemagglutinin (ha) of the 2009 pandemic influenza virus alter its pathogenesis and transmission. viral replication is increased in mammalian cells. infected mice show increased disease as measured by weight loss and lethality. transmission in ferrets is decreased in the presence of both substitutions, suggesting that amino acids 200t and 227e are adaptive changes in the ha of swine origin influenza viruses associated ... | 2013 | 23536663 |
| protective efficacy of in vitro synthesized, specific mrna vaccines against influenza a virus infection. | despite substantial improvements, influenza vaccine production-and availability-remain suboptimal. influenza vaccines based on mrna may offer a solution as sequence-matched, clinical-grade material could be produced reliably and rapidly in a scalable process, allowing quick response to the emergence of pandemic strains. here we show that mrna vaccines induce balanced, long-lived and protective immunity to influenza a virus infections in even very young and very old mice and that the vaccine rema ... | 2012 | 23159882 |
| decoding the distribution of glycan receptors for human-adapted influenza a viruses in ferret respiratory tract. | ferrets are widely used as animal models for studying influenza a viral pathogenesis and transmissibility. human-adapted influenza a viruses primarily target the upper respiratory tract in humans (infection of the lower respiratory tract is observed less frequently), while in ferrets, upon intranasal inoculation both upper and lower respiratory tract are targeted. viral tropism is governed by distribution of complex sialylated glycan receptors in various cells/tissues of the host that are specif ... | 2012 | 22359533 |
| ferret airway epithelial cell cultures support efficient replication of influenza b virus but not mumps virus. | ferrets have become the model animal of choice for influenza pathology and transmission experiments as they are permissive and susceptible to human influenza a viruses. however, inoculation of ferrets with mumps virus (muv) did not lead to successful infections. we evaluated the use of highly differentiated ferret tracheal epithelium cell cultures, fte, for predicting the potential of ferrets to support respiratory viral infections. fte cultures supported productive replication of human influenz ... | 2015 | 25953915 |
| pathogenic influenza b virus in the ferret model establishes lower respiratory tract infection. | influenza b viruses have become increasingly more prominent during influenza seasons. influenza b infection is typically considered a mild disease and receives less attention than influenza a, but has been causing 20 to 50 % of the total influenza incidence in several regions around the world. although there is increasing evidence of mid to lower respiratory tract diseases such as bronchitis and pneumonia in influenza b patients, little is known about the pathogenesis of recent influenza b virus ... | 2014 | 24989173 |
| detection of influenza c virus but not influenza d virus in scottish respiratory samples. | a newly proposed genus of influenza virus (influenza d) is associated with respiratory disease in pigs and cattle. the novel virus is most closely related to human influenza c virus and can infect ferrets but infection has not been reported in humans. | 2016 | 26655269 |
| isolation of a novel swine influenza virus from oklahoma in 2011 which is distantly related to human influenza c viruses. | of the orthomyxoviridae family of viruses, only influenza a viruses are thought to exist as multiple subtypes and has non-human maintenance hosts. in april 2011, nasal swabs were collected for virus isolation from pigs exhibiting influenza-like illness. subsequent electron microscopic, biochemical, and genetic studies identified an orthomyxovirus with seven rna segments exhibiting approximately 50% overall amino acid identity to human influenza c virus. based on its genetic organizational simila ... | 2013 | 23408893 |
| review of a new molecular virus pathotyping method in the context of bioterrorism. | avian influenza virus (aiv) and newcastle disease virus (ndv) infect various avian species including domestic poultry. clinical manifestations vary from subclinical or mild to severe multiorgan systemic disease with a near 100% mortality rate. severe disease is caused by highly virulent specific virus strains, termed highly pathogenic aiv and velogenic ndv. recent controversial influenza h5 adaptation studies in ferrets have highlighted the importance of preparedness against aiv as a bioterroris ... | 2013 | 23971812 |
| animal models for influenza virus pathogenesis, transmission, and immunology. | in humans, infection with an influenza a or b virus manifests typically as an acute and self-limited upper respiratory tract illness characterized by fever, cough, sore throat, and malaise. however, influenza can present along a broad spectrum of disease, ranging from sub-clinical or even asymptomatic infection to a severe primary viral pneumonia requiring advanced medical supportive care. disease severity depends upon the virulence of the influenza virus strain and the immune competence and pre ... | 2014 | 24709389 |
| pathogenic analysis of the pandemic 2009 h1n1 influenza a viruses in ferrets. | the pandemic 2009 h1n1 influenza a virus emerged in humans and caused the first influenza pandemic of the 21st century. mexican isolates, a/mexico/4108/2009 (h1n1) (mex4108) and a/mexico/indre4478/2009 (h1n1) (mex4487) derived from a mild case and from a cluster of severe cases, showed heterogeneity in virulence in a cynomolgus macaque model. to compare the more pathogenic differences, we generated recombinant viruses and compared their virulence in ferrets. ferrets infected with recombinant mex ... | 2017 | 28674309 |
| neuraminidase-based recombinant virus-like particles protect against lethal avian influenza a(h5n1) virus infection in ferrets. | avian influenza a (h5n1) viruses represent a growing threat for an influenza pandemic. the presence of widespread avian influenza virus infections further emphasizes the need for vaccine strategies for control of pre-pandemic h5n1 and other avian influenza subtypes. influenza neuraminidase (na) vaccines represent a potential strategy for improving vaccines against avian influenza h5n1 viruses. to evaluate a strategy for na vaccination, we generated a recombinant influenza virus-like particle (vl ... | 2017 | 28624679 |
| stockpiled pre-pandemic h5n1 influenza virus vaccines with as03 adjuvant provide cross-protection from h5n2 clade 2.3.4.4 virus challenge in ferrets. | avian influenza viruses, notably h5 subtype viruses, pose a continuous threat to public health due to their pandemic potential. in recent years, influenza virus h5 subtype split vaccines with novel oil-in-water emulsion based adjuvants (e.g. as03, mf59) have been shown to be safe, immunogenic, and able to induce broad immune responses in clinical trials, providing strong scientific support for vaccine stockpiling. however, whether such vaccines can provide protection from infection with emerging ... | 2017 | 28554058 |
| a novel a(h7n2) influenza virus isolated from a veterinarian caring for cats in a new york city animal shelter causes mild disease and transmits poorly in the ferret model. | in december 2016, a low-pathogenic avian influenza (lpai) a(h7n2) virus was identified to be the causative source of an outbreak in a cat shelter in new york city, which subsequently spread to multiple shelters in the states of new york and pennsylvania. one person with occupational exposure to infected cats became infected with the virus, representing the first lpai h7n2 virus infection in a human in north america since 2003. considering the close contact that frequently occurs between companio ... | 2017 | 28515300 |
| development of clade-specific and broadly reactive live attenuated influenza virus vaccines against rapidly evolving h5 subtype viruses. | we have developed pandemic live attenuated influenza vaccines (plaivs) against clade 1 h5n1 viruses on an ann arbor cold-adapted (ca) backbone that induced long-term immune memory. in 2015, many human infections caused by a new clade (clade 2.2.1.1) of goose/guangdong (gs/gd) lineage h5n1 viruses were reported in egypt, which prompted updating of the h5n1 plaiv. we explored two strategies to generate suitable plaivs. the first approach was to modify the hemagglutinin gene of a highly pathogenic ... | 2017 | 28490598 |
| a formulated tlr7/8 agonist is a flexible, highly potent and effective adjuvant for pandemic influenza vaccines. | since 1997, highly pathogenic avian influenza viruses of the h5n1 subtype have been transmitted from avian hosts to humans. the severity of h5n1 infection in humans, as well as the sporadic nature of h5n1 outbreaks, both geographically and temporally, make generation of an effective vaccine a global public health priority. an effective h5n1 vaccine must ultimately provide protection against viruses from diverse clades. toll-like receptor (tlr) agonist adjuvant formulations have a demonstrated ab ... | 2017 | 28429728 |
| the replication of bangladeshi h9n2 avian influenza viruses carrying genes from h7n3 in mammals. | h9n2 avian influenza viruses are continuously monitored by the world health organization because they are endemic; they continually reassort with h5n1, h7n9 and h10n8 viruses; and they periodically cause human infections. we characterized h9n2 influenza viruses carrying internal genes from highly pathogenic h7n3 viruses, which were isolated from chickens or quail from live-bird markets in bangladesh between 2010 and 2013. all of the h9n2 viruses used in this study carried mammalian host-specific ... | 2016 | 27094903 |
| selective bottlenecks shape evolutionary pathways taken during mammalian adaptation of a 1918-like avian influenza virus. | avian influenza virus reassortants resembling the 1918 human pandemic virus can become transmissible among mammals by acquiring mutations in hemagglutinin (ha) and polymerase. using the ferret model, we trace the evolutionary pathway by which an avian-like virus evolves the capacity for mammalian replication and airborne transmission. during initial infection, within-host ha diversity increased drastically. then, airborne transmission fixed two polymerase mutations that do not confer a detectabl ... | 2016 | 26867176 |
| mapping influenza transmission in the ferret model to transmission in humans. | the controversy surrounding 'gain-of-function' experiments on high-consequence avian influenza viruses has highlighted the role of ferret transmission experiments in studying the transmission potential of novel influenza strains. however, the mapping between influenza transmission in ferrets and in humans is unsubstantiated. we address this gap by compiling and analyzing 240 estimates of influenza transmission in ferrets and humans. we demonstrate that estimates of ferret secondary attack rate ( ... | 2015 | 26329460 |
| pandemic potential of avian influenza a (h7n9) viruses. | avian influenza viruses rarely infect humans, but the recently emerged avian h7n9 influenza viruses have caused sporadic infections in humans in china, resulting in 440 confirmed cases with 122 fatalities as of 16 may 2014. in addition, epidemiologic surveys suggest that there have been asymptomatic or mild human infections with h7n9 viruses. these viruses replicate efficiently in mammals, show limited transmissibility in ferrets and guinea pigs, and possess mammalian-adapting amino acid changes ... | 2014 | 25264312 |
| glycomic characterization of respiratory tract tissues of ferrets: implications for its use in influenza virus infection studies. | the initial recognition between influenza virus and the host cell is mediated by interactions between the viral surface protein hemagglutinin and sialic acid-terminated glycoconjugates on the host cell surface. the sialic acid residues can be linked to the adjacent monosaccharide by α2-3- or α2-6-type glycosidic bonds. it is this linkage difference that primarily defines the species barrier of the influenza virus infection with α2-3 binding being associated with avian influenza viruses and α2-6 ... | 2014 | 25135641 |
| circulating avian influenza viruses closely related to the 1918 virus have pandemic potential. | wild birds harbor a large gene pool of influenza a viruses that have the potential to cause influenza pandemics. foreseeing and understanding this potential is important for effective surveillance. our phylogenetic and geographic analyses revealed the global prevalence of avian influenza virus genes whose proteins differ only a few amino acids from the 1918 pandemic influenza virus, suggesting that 1918-like pandemic viruses may emerge in the future. to assess this risk, we generated and charact ... | 2014 | 24922572 |
| methods for evaluation of antiviral efficacy against influenza virus infections in animal models. | compounds undergoing preclinical development for anti-influenza virus activity require evaluation in small animal models. laboratory mice are most commonly used for initial studies because of size, cost, and availability. cotton rats, guinea pigs, and ferrets (particularly) have been used for more advanced studies. each animal infection model has certain limitations relative to human influenza infections. for example, the fever response that is evident in humans only occurs with consistency in f ... | 2013 | 23821285 |
| comparison of the levels of infectious virus in respirable aerosols exhaled by ferrets infected with influenza viruses exhibiting diverse transmissibility phenotypes. | influenza viruses pose a major public health burden to communities around the world by causing respiratory infections that can be highly contagious and spread rapidly through the population. despite extensive research on influenza viruses, the modes of transmission occurring most often among humans are not entirely clear. contributing to this knowledge gap is the lack of an understanding of the levels of infectious virus present in respirable aerosols exhaled from infected hosts. here, we used t ... | 2013 | 23658443 |
| engineering h5n1 avian influenza viruses to study human adaptation. | two studies of h5n1 avian influenza viruses that had been genetically engineered to render them transmissible between ferrets have proved highly controversial. divergent opinions exist about the importance of these studies of influenza transmission and about potential 'dual use' research implications. no consensus has developed yet about how to balance these concerns. after not recommending immediate full publication of earlier, less complete versions of the studies, the united states national s ... | 2012 | 22722191 |
| low pathogenic avian influenza isolates from wild birds replicate and transmit via contact in ferrets without prior adaptation. | direct transmission of avian influenza viruses to mammals has become an increasingly investigated topic during the past decade; however, isolates that have been primarily investigated are typically ones originating from human or poultry outbreaks. currently there is minimal comparative information on the behavior of the innumerable viruses that exist in the natural wild bird host. we have previously demonstrated the capacity of numerous north american avian influenza viruses isolated from wild b ... | 2012 | 22675507 |
| novel hemagglutinin nanoparticle influenza vaccine with matrix-m™ adjuvant induces hemagglutination inhibition, neutralizing, and protective responses in ferrets against homologous and drifted a(h3n2) subtypes. | influenza viruses frequently acquire mutations undergoing antigenic drift necessitating annual evaluation of vaccine strains. highly conserved epitopes have been identified in the hemagglutinin (ha) head and stem regions, however, current influenza vaccines induce only limited responses to these conserved sites. here, we describe a novel seasonal recombinant ha nanoparticle influenza vaccine (niv) formulated with a saponin-based adjuvant, matrix-m™. niv induced hemagglutination inhibition (hai) ... | 2017 | 28844407 |
| zoonotic risk, pathogenesis, and transmission of avian-origin h3n2 canine influenza virus. | two subtypes of influenza a virus (iav), avian-origin canine influenza virus h3n2 (civ-h3n2) and equine-origin civ-h3n8, are enzootic in the canine population. dogs have demonstrated seroconversion to diverse iavs and naturally occurring reassortants of civ-h3n2 and the 2009 h1n1 pandemic virus (pdmh1n1) have been isolated. we conducted a thorough phenotypic evaluation of civ-h3n2 in order to assess its threat to human health. using ferret-generated antisera we determined that civ-h3n2 is antige ... | 2017 | 28814512 |
| m2sr, a novel live influenza vaccine, protects mice and ferrets against highly pathogenic avian influenza. | the emergence of highly pathogenic avian influenza h5n1 viruses has heightened global concern about the threat posed by pandemic influenza. to address the need for a highly effective universal influenza vaccine, we developed a novel m2-deficient single replication (m2sr) influenza vaccine virus and previously reported that it provided strong heterosubtypic protection against seasonal influenza viruses in mice. in the current study, we assessed m2sr induced protection against h5n1 influenza in mi ... | 2017 | 28668565 |
| in vitro and in vivo evidence of a potential a(h1n1)pdm09 antigenic drift mediated by escape mutations in the haemagglutinin sa antigenic site. | influenza a(h1n1)pdm09 virus continues to circulate worldwide without evidence of significant antigenic drift between 2009 and 2016. by using escape mutants, we previously identified six haemagglutinin (ha) changes (t80r, g143e, g158e, n159d, k166e and a198e) that were located within antigenic sites. combinations of these mutations were introduced into the a(h1n1)pdm09 ha plasmid by mutagenesis. reassortant 6 : 2 viruses containing both the ha and na genes of the a(h1n1)pdm09 and the six interna ... | 2017 | 28631598 |
| inhibition of the infectivity and inflammatory response of influenza virus by arbidol hydrochloride in vitro and in vivo (mice and ferret). | influenza virus infections are the main contagious respiratory disease with high levels of morbidity and mortality worldwide. antiviral drugs are indispensable for the prophylaxis and treatment of influenza and other respiratory viral infections. in this study, the arbidol hydrochloride (arb), which has been licensed in russia and china, is used to investigate its anti-viral and anti-inflammatory efficacy in vitro and in vivo. the antiviral results in vitro showed that arb had a better inhibitio ... | 2017 | 28475918 |
| pathogenicity and transmission of a swine influenza a(h6n6) virus. | subtype h6 influenza a viruses (iavs) are commonly detected in wild birds and domestic poultry and can infect humans. in 2010, a h6n6 virus emerged in southern china, and since then, it has caused sporadic infections among swine. we show that this virus binds to α2,6-linked and α2,3-linked sialic acids. mutations at residues 222 (alanine to valine) and 228 (glycine to serine) of the virus hemagglutinin (ha) affected its receptor-binding properties. experiments showed that the virus has limited t ... | 2017 | 28400591 |
| an amino acid in the stalk domain of n1 neuraminidase is critical for enzymatic activity. | neuraminidase (na) is a sialidase expressed on the surface of influenza a viruses that releases progeny viruses from the surface of infected cells and prevents viruses becoming trapped in mucus. it is a homotetramer, with each monomer consisting of a transmembrane region, a stalk, and a globular head with sialidase activity. we recently characterized two swine viruses of the pandemic h1n1 lineage, a/swine/virginia/1814-1/2012 (ph1n1low-1) and a/swine/virginia/1814-2/2012 (ph1n1low-2), with almos ... | 2017 | 27847354 |
| impaired heterologous immunity in aged ferrets during sequential influenza a h1n1 infection. | the major burden of influenza morbidity resides within the elderly population. the challenge managing influenza-associated illness in the elderly is the decline of immune function, where mechanisms leading to immunological senescence have not been elucidated. to better represent the immune environment, we investigated clinical morbidity and immune function during sequential homologous and heterologous h1n1 influenza infection in an aged ferret model. our findings demonstrated experimentally that ... | 2014 | 25086242 |
| evaluation of recombinant 2009 pandemic influenza a (h1n1) viruses harboring zanamivir resistance mutations in mice and ferrets. | recombinant influenza a(h1n1)pdm09 wild-type (wt) and zanamivir-resistant e119g and q136k neuraminidase mutants were generated to determine their enzymatic and replicative properties in vitro, as well as their infectivity and transmissibility in mice and ferrets. viral titers of recombinant e119g and q136k mutants were significantly lower than those of the wt in the first 36 h postinoculation (p.i.) in vitro. the e119g and q136k mutations were both associated with a significant reduction of tota ... | 2013 | 23357777 |
| the potential of avian h1n1 influenza a viruses to replicate and cause disease in mammalian models. | h1n1 viruses in which all gene segments are of avian origin are the most frequent cause of influenza pandemics in humans; therefore, we examined the disease-causing potential of 31 avian h1n1 isolates of american lineage in dba/2j mice. thirty of 31 isolates were very virulent, causing respiratory tract infection; 22 of 31 resulted in fecal shedding; and 10 of 31 were as pathogenic as the pandemic 2009 h1n1 viruses. preliminary studies in balb/cj mice and ferrets showed that 1 of 4 isolates test ... | 2012 | 22848544 |
| pathogenicity and transmissibility of north american triple reassortant swine influenza a viruses in ferrets. | north american triple reassortant swine (trs) influenza a viruses have caused sporadic human infections since 2005, but human-to-human transmission has not been documented. these viruses have six gene segments (pb2, pb1, pa, ha, np, and ns) closely related to those of the 2009 h1n1 pandemic viruses. therefore, understanding of these viruses' pathogenicity and transmissibility may help to identify determinants of virulence of the 2009 h1n1 pandemic viruses and to elucidate potential human health ... | 2012 | 22829764 |
| pathogenicity testing of influenza candidate vaccine viruses in the ferret model. | the development of influenza candidate vaccine viruses (cvvs) for pre-pandemic vaccine production represents a critical step in pandemic preparedness. the multiple subtypes and clades of avian or swine origin influenza viruses circulating world-wide at any one time necessitates the continuous generation of cvvs to provide an advanced starting point should a novel zoonotic virus cross the species barrier and cause a pandemic. furthermore, the evolution and diversity of novel influenza viruses tha ... | 2017 | 28846898 |
| adjuvanted inactivated influenza a(h3n2) vaccines induce stronger immunogenicity in mice and confer higher protection in ferrets than unadjuvanted inactivated vaccines. | influenza viruses are major respiratory pathogens and the development of improved vaccines to prevent these infections is of high priority. here, we evaluated split inactivated a(h3n2) vaccines (a/uruguay/716/2007) combined or not with adjuvants (as03, as25 and protollin) and administered by three different routes, intramuscular (i.m.), intranasal (i.n.) or intradermal (i.d.), both in balb/c mice and in ferrets. ferrets were challenged with the homologous strain a/uruguay/716/2007 (h3n2) or the ... | 2014 | 25173481 |
| antigenic characterization of h3n2 influenza a viruses from ohio agricultural fairs. | the demonstrated link between the emergence of h3n2 variant (h3n2v) influenza a viruses (iavs) and swine exposure at agricultural fairs has raised concerns about the human health risk posed by iav-infected swine. understanding the antigenic profiles of iavs circulating in pigs at agricultural fairs is critical to developing effective prevention and control strategies. here, 68 h3n2 iav isolates recovered from pigs at ohio fairs (2009 to 2011) were antigenically characterized. these isolates were ... | 2013 | 23637412 |
| the hemagglutinin a stem antibody medi8852 prevents and controls disease and limits transmission of pandemic influenza viruses. | medi8852 is a novel monoclonal antibody (mab) that neutralizes both group i and group ii influenza a viruses (iavs) in vitro. we evaluated whether medi8852 was effective for prophylaxis and therapy against representative group i (h5n1) and group ii (h7n9) pandemic iavs in mice and ferrets and could be used to block transmission of influenza h1n1pdm09 in ferrets, compared to an irrelevant control mab r347 and oseltamivir. | 2017 | 28633457 |
| enhanced virulence of clade 2.3.2.1 highly pathogenic avian influenza a h5n1 viruses in ferrets. | sporadic avian to human transmission of highly pathogenic avian influenza (hpai) a(h5n1) viruses necessitates the analysis of currently circulating and evolving clades to assess their potential risk. following the spread and sustained circulation of clade 2 viruses across multiple continents, numerous subclades and genotypes have been described. to better understand the pathogenesis associated with the continued diversification of clade 2a(h5n1) influenza viruses, we investigated the relative vi ... | 2017 | 28038412 |
| economic analysis of pandemic influenza mitigation strategies for five pandemic severity categories. | the threat of emergence of a human-to-human transmissible strain of highly pathogenic influenza a(h5n1) is very real, and is reinforced by recent results showing that genetically modified a(h5n1) may be readily transmitted between ferrets. public health authorities are hesitant in introducing social distancing interventions due to societal disruption and productivity losses. this study estimates the effectiveness and total cost (from a societal perspective, with a lifespan time horizon) of a com ... | 2013 | 23496898 |
| assessment of pathogenicity and antigenicity of american lineage influenza h5n2 viruses in taiwan. | during december 2003 and march 2004, large scale epidemics of low-pathogenic avian influenza (lpai) h5n2 occurred in poultry farms in central and southern taiwan. based on genomic analysis, these h5n2 viruses contain ha and na genes of american-lineage h5n2 viruses and six internal genes from avian influenza a/h6n1 viruses endemic in poultry in taiwan. after disappearing for several years, these novel influenza h5n2 viruses caused outbreaks in poultry farms again in 2008, 2010 and 2012, and have ... | 2017 | 28549236 |
| carbohydrate fatty acid monosulphate esters are safe and effective adjuvants for humoral responses. | carbohydrate fatty acid sulphate esters (cfases) formulated in a squalane-in-water emulsion are effective adjuvants for humoral responses to a wide range of antigens in various animal species but rise in body temperature and local reactions albeit mild or minimal hampers application in humans. in rabbits, body temperature increased 1°c one day after intramuscular (im) injection, which returned to normal during the next day. the effect increased with increasing dose of cfase but not with the numb ... | 2017 | 28479181 |
| influenza-omics and the host response: recent advances and future prospects. | influenza a viruses (iav) continually evolve and have the capacity to cause global pandemics. because iav represents an ongoing threat, identifying novel therapies and host innate immune factors that contribute to iav pathogenesis is of considerable interest. this review summarizes the relevant literature as it relates to global host responses to influenza infection at both the proteome and transcriptome level. the various-omics infection systems that include but are not limited to ferrets, mice ... | 2017 | 28604586 |
| structure and function analysis of an antibody recognizing all influenza a subtypes. | influenza virus remains a threat because of its ability to evade vaccine-induced immune responses due to antigenic drift. here, we describe the isolation, evolution, and structure of a broad-spectrum human monoclonal antibody (mab), medi8852, effectively reacting with all influenza a hemagglutinin (ha) subtypes. medi8852 uses the heavy-chain vh6-1 gene and has higher potency and breadth when compared to other anti-stem antibodies. medi8852 is effective in mice and ferrets with a therapeutic wind ... | 2016 | 27453466 |
| a polyvalent influenza dna vaccine applied by needle-free intradermal delivery induces cross-reactive humoral and cellular immune responses in pigs. | pigs are natural hosts for influenza a viruses, and the infection is widely prevalent in swine herds throughout the world. current commercial influenza vaccines for pigs induce a narrow immune response and are not very effective against antigenically diverse viruses. to control influenza in pigs, the development of more effective swine influenza vaccines inducing broader cross-protective immune responses is needed. previously, we have shown that a polyvalent influenza dna vaccine using vectors c ... | 2016 | 27211039 |
| next-generation sequencing and bioinformatic approaches to detect and analyze influenza virus in ferrets. | conventional methods used to detect and characterize influenza viruses in biological samples face multiple challenges due to the diversity of subtypes and high dissimilarity of emerging strains. next-generation sequencing (ngs) is a powerful technique that can facilitate the detection and characterization of influenza, however, the sequencing strategy and the procedures of data analysis possess different aspects that require careful consideration. | 2014 | 24727517 |
| zanamivir conjugated to poly-l-glutamine is much more active against influenza viruses in mice and ferrets than the drug itself. | previously, polymer-attached zanamivir had been found to inhibit influenza a viruses in vitro far better than did small-molecule zanamivir (1) itself. the aim of this study was to identify in vitro-using the plaque reduction assay-a highly potent 1-polymer conjugate, and subsequently test its antiviral efficacy in vivo. | 2014 | 24065587 |
| considerations regarding appropriate sample size for conducting ferret transmission experiments. | evaluation of: nishiura h, yen h-l, cowling bj. sample size considerations for one-to-one animal transmission studies of the influenza a viruses. plos one 8(1), e55358 (2013). there is an urgent need to model in a laboratory setting the capacity of wild-type influenza viruses to transmit between mammals, to determine the molecular determinants and identify biological properties that confer influenza virus transmissibility, and to explore both pharmaceutical and nonpharmaceutical methods to inhib ... | 2013 | 23902143 |
| an in vivo human-plasmablast enrichment technique allows rapid identification of therapeutic influenza a antibodies. | recent advances enabling the cloning of human immunoglobulin g genes have proven effective for discovering monoclonal antibodies with therapeutic potential. however, these antibody-discovery methods are often arduous and identify only a few candidates from numerous antibody-secreting plasma cells or plasmablasts. we describe an in vivo enrichment technique that identifies broadly neutralizing human antibodies with high frequency. for this technique, human peripheral blood mononuclear cells from ... | 2013 | 23870317 |
| clinical profiles associated with influenza disease in the ferret model. | influenza a viruses continue to pose a threat to human health; thus, various vaccines and prophylaxis continue to be developed. testing of these products requires various animal models including mice, guinea pigs, and ferrets. however, because ferrets are naturally susceptible to infection with human influenza viruses and because the disease state resembles that of human influenza, these animals have been widely used as a model to study influenza virus pathogenesis. in this report, a statistical ... | 2013 | 23472182 |
| development of a neutralization assay for influenza virus using an endpoint assessment based on quantitative reverse-transcription pcr. | a microneutralization assay using an elisa-based endpoint assessment (elisa-mn) is widely used to measure the serological response to influenza virus infection and vaccination. we have developed an alternative microneutralization assay for influenza virus using a quantitative reverse transcription pcr-based endpoint assessment (qpcr-mn) in order to improve upon technical limitations associated with elisa-mn. for qpcr-mn, infected mdck-london cells in 96-well cell-culture plates are processed wit ... | 2013 | 23437084 |
| sample size considerations for one-to-one animal transmission studies of the influenza a viruses. | animal transmission studies can provide important insights into host, viral and environmental factors affecting transmission of viruses including influenza a. the basic unit of analysis in typical animal transmission experiments is the presence or absence of transmission from an infectious animal to a susceptible animal. in studies comparing two groups (e.g. two host genetic variants, two virus strains, or two arrangements of animal cages), differences between groups are evaluated by comparing t ... | 2013 | 23383167 |
| salicylate intoxication and influenza in ferrets. | a model of salicylate intoxication was developed in ferrets to permit the evaluation of the interaction with viruses isolated from patients with reye's syndrome. salicylate intoxication produced a mild elevation of the serum glutamic oxaloacetic transaminase and fatty changes in the liver, but these changes differed from those seen in reye's syndrome on light and electron microscopy. salicylates were associated with decreased activity of hepatic phosphorylase and a slight depression of activity ... | 1979 | 432001 |
| comparison of neutralizing activity in nasal secretion and serum of ferrets in response to infection with influenza a viruses. | | 1973 | 4692625 |