Publications

TitleAbstractYear(sorted descending)
Filter
PMID
Filter
dose-response time modeling for highly pathogenic avian influenza a (h5n1) virus infection.aims: to develop time-dependent dose-response models for highly pathogenic avian influenza a (hpai) of the h5n1 subtype virus. methods and results: a total of four candidate time-dependent dose-response models were fitted to four survival data sets for animals (mice or ferrets) exposed to graded doses of hpai h5n1 virus using the maximum likelihood estimation. a beta-poisson dose-response model with the n(50) parameter modified by an exponential-inverse-power time dependency or an exponential ...201121790679
genetic characterization and pathogenicity assessment of highly pathogenic h5n1 avian influenza viruses isolated from migratory wild birds in 2011, south korea.the continued spread of a highly pathogenic avian influenza (hpai) h5n1 virus among wild birds and poultry has posed a potential threat to human public health. in the present study, we report the isolation of hpai h5n1 viruses (a/md/korea/w401/11 and a/md/korea/w404/11) from fecal samples of migratory birds. genetic and phlyogenetic analyses demonstrated that these viruses are genetically identical possessing gene segments from avian virus origin and showing highest sequence similarities (as hig ...201121782862
transmissibility of pandemic h1n1 and genetically related swine influenza viruses in ferrets. 201121751464
influenza h5 hemagglutinin dna primes the antibody response elicited by the live attenuated influenza a/vietnam/1203/2004 vaccine in ferrets.priming immunization plays a key role in protecting individuals or populations to influenza viruses that are novel to humans. to identify the most promising vaccine priming strategy, we have evaluated different prime-boost regimens using inactivated, dna and live attenuated vaccines in ferrets. live attenuated influenza a/vietnam/1203/2004 (h5n1) candidate vaccine (laiv, vn04 ca) primed ferrets efficiently while inactivated h5n1 vaccine could not prime the immune response in seronegative ferrets ...201121760928
compatibility of h9n2 avian influenza surface genes and 2009 pandemic h1n1 internal genes for transmission in the ferret model.in 2009, a novel h1n1 influenza (ph1n1) virus caused the first influenza pandemic in 40 y. the virus was identified as a triple reassortant between avian, swine, and human influenza viruses, highlighting the importance of reassortment in the generation of viruses with pandemic potential. previously, we showed that a reassortant virus composed of wild-type avian h9n2 surface genes in a seasonal human h3n2 backbone could gain efficient respiratory droplet transmission in the ferret model. here we ...201121730147
hemagglutinin-neuraminidase balance confers respiratory-droplet transmissibility of the pandemic h1n1 influenza virus in ferrets.a novel reassortant derived from north american triple-reassortant (trsw) and eurasian swine (easw) influenza viruses acquired sustained human-to-human transmissibility and caused the 2009 influenza pandemic. to identify molecular determinants that allowed efficient transmission of the pandemic h1n1 virus among humans, we evaluated the direct-contact and respiratory-droplet transmissibility in ferrets of representative swine influenza viruses of different lineages obtained through a 13-y surveil ...201121825167
role of permissive neuraminidase mutations in influenza a/brisbane/59/2007-like (h1n1) viruses.neuraminidase (na) mutations conferring resistance to na inhibitors were believed to compromise influenza virus fitness. unexpectedly, an oseltamivir-resistant a/brisbane/59/2007 (bris07)-like h1n1 h275y na variant emerged in 2007 and completely replaced the wild-type (wt) strain in 2008-2009. the na of such variant contained additional na changes (r222q, v234m and d344n) that potentially counteracted the detrimental effect of the h275y mutation on viral fitness. here, we rescued a recombinant b ...201122174688
novel reassortment of eurasian avian-like and pandemic/2009 influenza viruses in swine: infectious potential for humans.pigs are considered to be intermediate hosts and "mixing vessels," facilitating the genesis of pandemic influenza viruses, as demonstrated by the emergence of the 2009 h1n1 pandemic (pdm/09) virus. the prevalence and repeated introduction of the pdm/09 virus into pigs raises the possibility of generating novel swine influenza viruses with the potential to infect humans. to address this, an active influenza surveillance program was conducted with slaughtered pigs in abattoirs in southern china. o ...201121849442
Generation of recombinant pandemic H1N1 influenza virus with the HA cleavable by bromelain and identification of the residues influencing HA bromelain cleavage.The proteolytic enzyme bromelain has been traditionally used to cleave the hemagglutinin (HA) protein at the C-terminus of the HA2 region to release the HA proteins from influenza virions. The bromelain cleaved HA (BHA) has been routinely used as an antigen to generate antiserum that is essential for influenza vaccine product release. The HA of the 2009 pandemic H1N1 influenza A/California/7/2009 (CA09) virus could not be cleaved efficiently by bromelain. To ensure timely delivery of BHA for ant ...201122172510
Neuropathology of H5N1 virus infection in ferrets.Highly pathogenic H5N1 virus remains a potential threat to humans. Over 289 fatalities have been reported in WHO confirmed human cases since 2003, and lack of effective vaccines and early treatments contribute to increasing numbers of cases and fatalities. H5N1 encephalitis is a recognized cause of death in Vietnamese cases, and brain pathology is described in other human cases and naturally infected animals. However, neither pathogenesis of H5N1 viral infection in human brain nor post-infection ...201122176758
avian and human influenza a virus receptors in trachea and lung of animals.influenza a viruses are capable of crossing the specific barrier between human beings and animals resulting in interspecies transmission. the important factor of potential infectivity of influenza a viruses is the suitability of the receptor binding site of the host and viruses. the affinities of avian and human influenza virus to bind with the receptors and the distributions of receptors in animals are different.201021337915
a nonlethal young domesticated ferret (mustela putorius furo) model for studying pandemic influenza virus a/california/04/2009 (h1n1).recent events have heightened the need for the rapid development of vaccines directed against pandemic influenza h1n1 viruses circulating during 2009 to 2010. the current study was conducted to establish a virus challenge dose for a subsequent ca/04 vaccine efficacy study in 3-mo-old domesticated ferrets. an additional consideration in using ca/04 in ferrets is the selection of endpoints on which to base the challenge dose, given the potential nonlethality of this particular model. four doses ra ...201021262121
effect of the neuraminidase mutation h274y conferring resistance to oseltamivir on the replicative capacity and virulence of old and recent human influenza a(h1n1) viruses.the viral fitness of neuraminidase inhibitor (nai)-resistant influenza viruses is believed to be impaired. unexpectedly, an oseltamivir-resistant a(h1n1) variant containing the h274y neuraminidase (na) mutation recently disseminated worldwide, suggesting that the replication and virulence properties of this mutant virus were not compromised.201020100088
severity of pneumonia due to new h1n1 influenza virus in ferrets is intermediate between that due to seasonal h1n1 virus and highly pathogenic avian influenza h5n1 virus.the newly emerged influenza a(h1n1) virus (new h1n1 virus) is causing the first influenza pandemic of this century. three influenza pandemics of the previous century caused variable mortality, which largely depended on the development of severe pneumonia. however, the ability of the new h1n1 virus to cause pneumonia is poorly understood.201020187747
influenza h1n1 a/solomon island/3/06 virus receptor binding specificity correlates with virus pathogenicity, antigenicity, and immunogenicity in ferrets.influenza viruses attach to cells via a sialic acid moiety (sialic acid receptor) that is alpha2-3 linked or alpha2-6 linked to galactose (alpha2-3sal or alpha2-6sal); sialic acid acts as a receptor for the virus. using lectin staining, we demonstrated that the alpha2-6sal configuration is predominant in the respiratory tract of ferrets, including trachea, bronchus, and lung alveolus tissues. recombinant wild-type (rwt) influenza a/solomon island/3/06 (si06) (h1n1) viruses were constructed to as ...201020200248
mutations in the ns1 c-terminal tail do not enhance replication or virulence of the 2009 pandemic h1n1 influenza a virus.the 'classical' swine h1n1 influenza a virus lineage was established after the devastating 1918 human pandemic virus entered domestic pig herds. a descendent of this lineage recently re-emerged in humans as the 2009 pandemic h1n1 virus. adaptation in pigs has led to several changes in the multifunctional viral ns1 protein as compared with the parental 1918 virus, most notably a k217e substitution that abolishes binding to host crk/crkl signalling adapters, and an 11 aa c-terminal truncation. usi ...201020237225
detection of influenza a and b neutralizing antibodies in vaccinated ferrets and macaques using specific biotin-streptavidin conjugated antibodies.several critical factors of an influenza microneutralization assay, utilizing a rapid biotin-streptavidin conjugated system for detecting influenza virus subtypes a and b, are addressed within this manuscript. factors such as incubation times, amount of virus, cell seeding, sonication, and tpck trypsin were evaluated for their ability to affect influenza virus neutralization in a microplate-based neutralization assay using madin-darby canine kidney (mdck) cells. it is apparent that the amount of ...201019913054
animal models for the preclinical evaluation of candidate influenza vaccines.at present, new influenza a (h1n1)2009 viruses of swine origin are responsible for the first influenza pandemic of the 21st century. in addition, highly pathogenic avian influenza a/h5n1 viruses continue to cause outbreaks in poultry and, after zoonotic transmission, cause an ever-increasing number of human cases, of which 59% have a fatal clinical outcome. it is also feared that these viruses adapt to replication in humans and become transmissible from human to human. the development of effecti ...201020021306
modeling host responses in ferrets during a/california/07/2009 influenza infection.immune responses during infection with pandemic h1n1 2009 influenza a virus (2009-h1n1) are still poorly understood. using an experimental infection model in ferrets, we examined the pathological features and characterized the host immune responses by using microarray analysis, during infection with 2009-h1n1 a/california/07/2009 and seasonal a/brisbane/59/2007. chemokines ccl2, ccl8, cxcl7 and cxcl10 along with the majority of interferon-stimulated genes were expressed early, correlated to lung ...201020334888
rapid selection of a transmissible multidrug-resistant influenza a/h3n2 virus in an immunocompromised host.the overall impact of influenza virus infection in immunocompromised patients is largely unknown. antigenic drift and genetic variations during prolonged influenza infection have been demonstrated. in this report we describe a multidrug-resistant h3n2 influenza virus isolated from an immunocompromised patient after 5 days of therapy.201020350163
comparative efficacy of hemagglutinin, nucleoprotein, and matrix 2 protein gene-based vaccination against h5n1 influenza in mouse and ferret.efforts to develop a broadly protective vaccine against the highly pathogenic avian influenza a (hpai) h5n1 virus have focused on highly conserved influenza gene products. the viral nucleoprotein (np) and ion channel matrix protein (m2) are highly conserved among different strains and various influenza a subtypes. here, we investigate the relative efficacy of np and m2 compared to ha in protecting against hpai h5n1 virus. in mice, previous studies have shown that vaccination with np and m2 in re ...201020352112
in vitro assessment of attachment pattern and replication efficiency of h5n1 influenza a viruses with altered receptor specificity.the continuous circulation of the highly pathogenic avian influenza (hpai) h5n1 virus has been a cause of great concern. the possibility of this virus acquiring specificity for the human influenza a virus receptor, alpha2,6-linked sialic acids (sa), and being able to transmit efficiently among humans is a constant threat to human health. different studies have described amino acid substitutions in hemagglutinin (ha) of clinical hpai h5n1 isolates or that were introduced experimentally that resul ...201020392847
the impact of key amino acid substitutions in the hemagglutinin of influenza a (h3n2) viruses on vaccine production and antibody response.influenza h3n2 viruses have recently drifted from a/wisconsin/67/05-like to a/brisbane/10/07-like viruses. the effect of key amino acid substitutions in the hemagglutinin (ha) protein on the replication, antigenicity and immunogenicity of cold-adapted, live attenuated vaccine strains was examined. a/brisbane/10/07 egg isolate contained a unique combination of g186 and p194 which were required for efficient virus growth in madin-darby canine kidney (mdck) cells and embryonated chicken eggs, but t ...201020399830
neuraminidase receptor binding variants of human influenza a(h3n2) viruses resulting from substitution of aspartic acid 151 in the catalytic site: a role in virus attachment?changes in the receptor binding characteristics of human h3n2 viruses have been evident from changes in the agglutination of different red blood cells (rbcs) and the reduced growth capacity of recently isolated viruses, particularly in embryonated eggs. an additional peculiarity of viruses circulating in 2005 to 2009 has been the poor inhibition of hemagglutination by postinfection ferret antisera for many viruses isolated in mdck cells, including homologous reference viruses. this was shown not ...201020410266
glycosylation at 158n of the hemagglutinin protein and receptor binding specificity synergistically affect the antigenicity and immunogenicity of a live attenuated h5n1 a/vietnam/1203/2004 vaccine virus in ferrets.a live attenuated influenza a/vietnam/1203/2004 (h5n1) vaccine virus (vn04 ca) has receptor binding specificity to alpha2,3-linked sialosides (alpha2,3sal), and a single dose induces a minimal serum antibody response in mice and ferrets. in contrast, a/hong kong/213/2003 (h5n1) vaccine virus (hk03 ca) binds to both alpha2,6sal and alpha2,3sal and generates a stronger serum antibody response in animals. among the 9 amino acids that differed between the two h5 ha1 proteins, several hk03-specific r ...201020427525
inefficient control of host gene expression by the 2009 pandemic h1n1 influenza a virus ns1 protein.in 2009, a novel swine-origin h1n1 influenza a virus emerged. here, we characterize the multifunctional ns1 protein of this human pandemic virus in order to understand factors that may contribute to replication efficiency or pathogenicity. although the 2009 h1n1 virus ns1 protein (2009/ns1) is an effective interferon antagonist, we found that this ns1 (unlike those of previous human-adapted influenza a viruses) is unable to block general host gene expression in human or swine cells. this propert ...201020444891
recombinant h1n1 virus-like particle vaccine elicits protective immunity in ferrets against the 2009 pandemic h1n1 influenza virus.the pandemic virus of 2009 (2009 h1n1) continues to cause illness worldwide, especially in younger age groups. the widespread h1n1 virus infection further emphasizes the need for vaccine strategies that are effective against emerging pandemic viruses and are not dependent on the limitations of traditional egg-based technology. this report describes a recombinant influenza virus-like particle (vlp) vaccine consisting of hemagglutinin (ha), neuraminidase (na), and matrix (m1) proteins of influenza ...201020470801
establishment and characterization of a madin-darby canine kidney reporter cell line for influenza a virus assays.influenza virus diagnosis has traditionally relied on virus isolation in chicken embryo or cell cultures. many laboratories have adopted rapid molecular methods for detection of influenza viruses and discontinued routine utilization of the relatively slow viral culture methods. we describe an influenza a virus reporter cell line that contributes to more efficient viral detection in cell culture. madin-darby canine kidney (mdck) cells were engineered to constitutively produce an influenza virus g ...201020504984
a single immunization with covaccine ht-adjuvanted h5n1 influenza virus vaccine induces protective cellular and humoral immune responses in ferrets.highly pathogenic avian influenza a viruses of the h5n1 subtype continue to circulate in poultry, and zoonotic transmissions are reported frequently. since a pandemic caused by these highly pathogenic viruses is still feared, there is interest in the development of influenza a/h5n1 virus vaccines that can protect humans against infection, preferably after a single vaccination with a low dose of antigen. here we describe the induction of humoral and cellular immune responses in ferrets after vacc ...201020519384
assessing the development of oseltamivir and zanamivir resistance in a(h5n1) influenza viruses using a ferret model.using an in vivo ferret model, we investigated the development of resistance to oseltamivir and zanamivir for two different influenza a(h5n1) viruses (a/vietnam/1203/2004, haemagglutinin phylogenetic clade 1, and a/chicken/laos/26/2006, haemagglutinin phylogenetic clade 2.3) by treating the animals with doses equivalent either to the recommended human treatment dose or a range of sub-optimal drug doses. no resistance was observed in oseltamivir-treated ferrets, but analysis of nasal washes from ...201020603155
course of seasonal influenza a/brisbane/59/07 h1n1 infection in the ferret.every year, influenza viruses infect approximately 5-20% of the population in the united states leading to over 200,000 hospitalizations and 36,000 deaths from flu-related complications. in this study, we characterized the immune and pathological progression of a seasonal strain of h1n1 influenza virus, a/brisbane/59/2007 in a ferret model. the immune response of the animals showed a dose-dependent increase with increased virus challenge, as indicated by the presence of virus specific igg, igm, ...201020618974
an influenza a/h1n1/2009 hemagglutinin vaccine produced in escherichia coli.the a/h1n1/2009 influenza pandemic made evident the need for faster and higher-yield methods for the production of influenza vaccines. platforms based on virus culture in mammalian or insect cells are currently under investigation. alternatively, expression of fragments of the hemagglutinin (ha) protein in prokaryotic systems can potentially be the most efficacious strategy for the manufacture of large quantities of influenza vaccine in a short period of time. despite experimental evidence on th ...201020661476
comparative pathology of select agent influenza a virus infections.influenza a virus infections may spread rapidly in human populations and cause variable mortality. two of these influenza viruses have been designated as select agents: 1918 h1n1 virus and highly pathogenic avian influenza (hpai) virus. knowledge of the pathology of these virus infections in humans, other naturally infected species, and experimental animals is important to understand the pathogenesis of influenza, to design appropriate models for evaluation of medical countermeasures, and to mak ...201020682805
recombinant soluble, multimeric ha and na exhibit distinctive types of protection against pandemic swine-origin 2009 a(h1n1) influenza virus infection in ferrets.the emergence and subsequent swift and global spread of the swine-origin influenza virus a(h1n1) in 2009 once again emphasizes the strong need for effective vaccines that can be developed rapidly and applied safely. with this aim, we produced soluble, multimeric forms of the 2009 a(h1n1) ha (sha(3)) and na (sna(4)) surface glycoproteins using a virus-free mammalian expression system and evaluated their efficacy as vaccines in ferrets. immunization twice with 3.75-microg doses of these antigens e ...201020686020
multiple infections with seasonal influenza a virus induce cross-protective immunity against a(h1n1) pandemic influenza virus in a ferret model.an age bias toward children and young adults has been reported for infection and hospitalizations with pandemic h1n1 influenza (a[h1n1]pdm) in the 2009 and 2010 influenza seasons in the southern and northern hemispheres. serological analysis of prepandemic samples has shown a higher incidence of cross-reactive antibodies to a(h1n1)pdm virus in older populations; conserved t cell epitopes between viruses have been identified. the contribution of preexisting immunity to seasonal influenza to prote ...201020715930
evaluation of a modified vaccinia virus ankara (mva)-based candidate pandemic influenza a/h1n1 vaccine in the ferret model.the zoonotic transmissions of highly pathogenic avian influenza viruses of the h5n1 subtype that have occurred since 1997 have sparked the development of novel influenza vaccines. the advent of reverse genetics technology, cell-culture production techniques and novel adjuvants has improved the vaccine strain preparation, production process and immunogenicity of the vaccines, respectively, and has accelerated the availability of pandemic influenza vaccines. however, there is still room for improv ...201020719991
oseltamivir-resistant variants of the 2009 pandemic h1n1 influenza a virus are not attenuated in the guinea pig and ferret transmission models.oseltamivir is routinely used worldwide for the treatment of severe influenza a virus infection, and should drug-resistant pandemic 2009 h1n1 viruses become widespread, this potent defense strategy might fail. oseltamivir-resistant variants of the pandemic 2009 h1n1 influenza a virus have been detected in a substantial number of patients, but to date, the mutant viruses have not moved into circulation in the general population. it is not known whether the resistance mutations in viral neuraminid ...201020739532
natural cases of 2009 pandemic h1n1 influenza a virus in pet ferrets.respiratory swab samples were collected from 5 pet ferrets (mustela putorius furo) exhibiting influenza-like illness. the ferrets represented 3 households in 2 states. in each case, the owners reported influenza-like illness in themselves or family members prior to the onset of a similar illness in the ferrets. real-time reverse transcription polymerase chain reaction assays designed for the detection of the 2009 h1n1 influenza a virus were conducted in the state animal health laboratories. the ...201020807944
ferrets develop fatal influenza after inhaling small particle aerosols of highly pathogenic avian influenza virus a/vietnam/1203/2004 (h5n1).there is limited knowledge about the potential routes for h5n1 influenza virus transmission to and between humans, and it is not clear whether humans can be infected through inhalation of aerosolized h5n1 virus particles. ferrets are often used as a animal model for humans in influenza pathogenicity and transmissibility studies. in this manuscript, a nose-only bioaerosol inhalation exposure system that was recently developed and validated was used in an inhalation exposure study of aerosolized a ...201020843329
virulence-associated substitution d222g in the hemagglutinin of 2009 pandemic influenza a(h1n1) virus affects receptor binding.the clinical impact of the 2009 pandemic influenza a(h1n1) virus (pdmh1n1) has been relatively low. however, amino acid substitution d222g in the hemagglutinin of pdmh1n1 has been associated with cases of severe disease and fatalities. d222g was introduced in a prototype pdmh1n1 by reverse genetics, and the effect on virus receptor binding, replication, antigenic properties, and pathogenesis and transmission in animal models was investigated. pdmh1n1 with d222g caused ocular disease in mice with ...201020844044
the ha and ns genes of human h5n1 influenza a virus contribute to high virulence in ferrets.highly pathogenic h5n1 influenza a viruses have spread across asia, europe, and africa. more than 500 cases of h5n1 virus infection in humans, with a high lethality rate, have been reported. to understand the molecular basis for the high virulence of h5n1 viruses in mammals, we tested the virulence in ferrets of several h5n1 viruses isolated from humans and found a/vietnam/ut3062/04 (ut3062) to be the most virulent and a/vietnam/ut3028/03 (ut3028) to be avirulent in this animal model. we then ge ...201020862325
characterization of oseltamivir-resistant 2009 h1n1 pandemic influenza a viruses.influenza viruses resistant to antiviral drugs emerge frequently. not surprisingly, the widespread treatment in many countries of patients infected with 2009 pandemic influenza a (h1n1) viruses with the neuraminidase (na) inhibitors oseltamivir and zanamivir has led to the emergence of pandemic strains resistant to these drugs. sporadic cases of pandemic influenza have been associated with mutant viruses possessing a histidine-to-tyrosine substitution at position 274 (h274y) in the na, a mutatio ...201020865125
classical swine h1n1 influenza viruses confer cross protection from swine-origin 2009 pandemic h1n1 influenza virus infection in mice and ferrets.the hemagglutinin of the 2009 pandemic h1n1 influenza virus is a derivative of and is antigenically related to classical swine but not to seasonal human h1n1 viruses. we compared the a/california/7/2009 (ca/7/09) virus recommended by the who as the reference virus for vaccine development, with two classical swine influenza viruses a/swine/iowa/31 (sw/ia/31) and a/new jersey/8/1976 (nj/76) to establish the extent of immunologic cross-reactivity and cross-protection in animal models. primary infec ...201020926110
ns-based live attenuated h1n1 pandemic vaccines protect mice and ferrets.although vaccines against influenza a virus are the most effective method to combat infection, it is clear that their production needs to be accelerated and their efficacy improved. we generated live attenuated human influenza a vaccines (laivs) by rationally engineering mutations directly into the genome of a pandemic-h1n1 virus. two laivs (ns1-73 and ns1-126) were based on the success of laivs for animal influenza a viruses. a third candidate (nsĪ“5) is a unique ns-mutant that has never been us ...201020934458
rapid detection of the pandemic 2009 h1n1 virus m gene by real-time and gel-based rt-pcr assays.since the first pandemic 2009 h1n1 (ph1n1) virus was isolated from humans, it has also been detected in other mammalian (pigs, cats, dogs, ferrets) and avian (turkey) species, most likely because of cross-species transmission from humans. the ph1n1 contains six genes derived from swine influenza viruses (sivs) currently circulating in north america of human- (pb1), avian- (pb2, pa), and swine- (ha, np, and ns) origin and two genes (na and m) derived from eurasian sivs. the novel genetic composit ...201020958934
contemporary seasonal influenza a (h1n1) virus infection primes for a more robust response to split inactivated pandemic influenza a (h1n1) virus vaccination in ferrets.human influenza pandemics occur when influenza viruses to which the population has little or no immunity emerge and acquire the ability to achieve human-to-human transmission. in april 2009, cases of a novel h1n1 influenza virus in children in the southwestern united states were reported. it was retrospectively shown that these cases represented the spread of this virus from an ongoing outbreak in mexico. the emergence of the pandemic led to a number of national vaccination programs. surprisingl ...201020962210
antibody responses induced by japanese whole inactivated vaccines against equine influenza virus (h3n8) belonging to florida sublineage clade2.in 2010, the world organisation for animal health recommended the inclusion of a florida sublineage clade2 strain of equine influenza virus (h3n8), which is represented by a/equine/richmond/1/07 (richmond07), in equine influenza vaccines. here, we evaluate the antigenic differences between japanese vaccine strains and richmond07 by performing hemagglutination inhibition (hi) assays. ferret antiserum raised to a/equine/la plata/93 (la plata93), which is a japanese vaccine strain, reacted with ric ...201021099188
immunogenicity and protective efficacy of a live attenuated vaccine against the 2009 pandemic a h1n1 in mice and ferrets.a novel 2009 influenza a (h1n1) virus was transmitted from humans to humans worldwide. the live attenuated monovalent a h1n1 vaccine (lamv) for intranasal administration has shown promising immunogenicity and safety in clinical trials and for human use, but the experimental data based on lamv is incomplete. in this study, using reverse genetic technology, we produced a cold-adapted (ca), live attenuated bj/aa ca that contained hemagglutinin (ha) and neuraminidase (na) genes from a 2009 pandemic ...201021111782
genetic immunization in the lung induces potent local and systemic immune responses.successful vaccination against respiratory infections requires elicitation of high levels of potent and durable humoral and cellular responses in the lower airways. to accomplish this goal, we used a fine aerosol that targets the entire lung surface through normal respiration to deliver replication-incompetent recombinant adenoviral vectors expressing gene products from several infectious pathogens. we show that this regimen induced remarkably high and stable lung t-cell responses in nonhuman pr ...201021135247
seasonal influenza vaccination and the risk of infection with pandemic influenza: a possible illustration of non-specific temporary immunity following infection.four canadian studies have suggested that receipt of seasonal influenza vaccine increased the risk of laboratory-confirmed infection with 2009 pandemic influenza a(h1n1). during the influenza season of 2009 in victoria, australia, this virus comprised 97% of all circulating influenza viruses for which sub-typing was available. we found no evidence that seasonal influenza vaccine increased the risk of, or provided protection against, infection with the pandemic virus. ferret experiments have sugg ...201021144441
preclinical and clinical development of plant-made virus-like particle vaccine against avian h5n1 influenza.the recent swine h1n1 influenza outbreak demonstrated that egg-based vaccine manufacturing has an achille's heel: its inability to provide a large number of doses quickly. using a novel manufacturing platform based on transient expression of influenza surface glycoproteins in nicotiana benthamiana, we have recently demonstrated that a candidate virus-like particle (vlp) vaccine can be generated within 3 weeks of release of sequence information. herein we report that alum-adjuvanted plant-made vl ...201021203523
multidrug-resistant 2009 pandemic influenza a(h1n1) viruses maintain fitness and transmissibility in ferrets.the 2009 influenza a(h1n1) pandemic called attention to the limited influenza treatment options available, especially in individuals at high risk of severe disease. neuraminidase inhibitor-resistant seasonal h1n1 viruses have demonstrated the ability to transmit well despite early data indicating that resistance reduces viral fitness. 2009 h1n1 pandemic viruses have sporadically appeared containing resistance to neuraminidase inhibitors and the adamantanes, but the ability of these viruses to re ...201021208927
avian influenza in birds and mammals.the disease syndromes caused by avian influenza viruses are highly variable depending on the host species infected, its susceptibility and response to infection and the virulence of the infecting viral strain. although avian influenza viruses have a broad host range in general, it is rare for an individual strain or subtype to infect more than one species. the h5n1 highly pathogenic avian influenza virus (hpaiv) lineages of viruses that descended from a/goose/guandong/96 (h5n1 hpaiv) are unusual ...200918485480
evaluation of live attenuated influenza a virus h6 vaccines in mice and ferrets.avian influenza a virus a/teal/hk/w312/97 (h6n1) possesses seven gene segments that are highly homologous to those of highly pathogenic human influenza h5n1 viruses, suggesting that a w312-like h6n1 virus might have been involved in the generation of the a/hk/97 h5n1 viruses. the continuous circulation and reassortment of influenza h6 subtype viruses in birds highlight the need to develop an h6 vaccine to prevent potential influenza pandemics caused by the h6 viruses. based on the serum antibody ...200918945773
plant-derived hemagglutinin protects ferrets against challenge infection with the a/indonesia/05/05 strain of avian influenza.the global spread of highly pathogenic avian influenza virus (h5n1 subtype) has promoted efforts to develop human vaccines against potential pandemic outbreaks. however, current platforms for influenza vaccine production are cumbersome, limited in scalability and often require the handling of live infectious virus. we describe the production of hemagglutinin from the a/indonesia/05/05 strain of h5n1 influenza virus by transient expression in plants, and demonstrate the immunogenicity and protect ...200919100806
viral rna polymerase complex promotes optimal growth of 1918 virus in the lower respiratory tract of ferrets.the 1918 influenza pandemic was the most devastating outbreak of infectious disease in human history, accounting for about 50 million deaths worldwide. in addition to a significant number of cases of secondary bacterial pneumonia, this highly pathogenic strain of influenza a virus caused fatal primary viral pneumonia. to identify the viral gene(s) chiefly responsible for the high virulence of the 1918 virus, we generated a series of reassortants between the 1918 virus and a contemporary human h1 ...200919114663
intranasal administration of alpha interferon reduces seasonal influenza a virus morbidity in ferrets.the type i interferon (ifn) response represents one of the first lines of defense against influenza virus infections. in this study, we assessed the protective potential of exogenous ifn-alpha against seasonal and highly pathogenic influenza viruses in ferrets. intranasal treatment with ifn-alpha several hours before infection with the h1n1 influenza a virus strain a/ussr/90/77 reduced viral titers in nasal washes at least 100-fold compared to mock-treated controls. ifn-treated animals developed ...200919193792
h5n1 vaccine-specific b cell responses in ferrets primed with live attenuated seasonal influenza vaccines.live attenuated influenza h5n1 vaccines have been produced and evaluated in mice and ferrets that were never exposed to influenza a virus infection (suguitan et al., plos medicine, e360:1541, 2006). however, the preexisting influenza heterosubtypic immunity on live attenuated h5n1 vaccine induced immune response has not been evaluated.200919209231
human ha and polymerase subunit pb2 proteins confer transmission of an avian influenza virus through the air.the influenza virus genes that confer efficient transmission of epidemic and pandemic strains in humans have not been identified. the rapid spread and severe disease caused by the 1918 influenza pandemic virus makes it an ideal virus to study the transmissibility of potentially pandemic influenza strains. here, we used a series of human 1918-avian h1n1 influenza reassortant viruses to identify the genetic determinants that govern airborne transmission of avian influenza viruses. we have demonstr ...200919211790
experimental infection of pigs with the human 1918 pandemic influenza virus.swine influenza was first recognized as a disease entity during the 1918 "spanish flu" pandemic. the aim of this work was to determine the virulence of a plasmid-derived human 1918 pandemic h1n1 influenza virus (reconstructed 1918, or 1918/rec, virus) in swine using a plasmid-derived a/swine/iowa/15/1930 h1n1 virus (1930/rec virus), representing the first isolated influenza virus, as a reference. four-week-old piglets were inoculated intratracheally with either the 1930/rec or the 1918/rec virus ...200919224986
the public health impact of avian influenza viruses.influenza viruses with novel hemagglutinin and 1 or more accompanying genes derived from avian influenza viruses sporadically emerge in humans and have the potential to result in a pandemic if the virus causes disease and spreads efficiently in a population that lacks immunity to the novel hemagglutinin. since 1997, multiple avian influenza virus subtypes have been transmitted directly from domestic poultry to humans and have caused a spectrum of human disease, from asymptomatic to severe and fa ...200919276438
isolation and genetic characterization of h5n2 influenza viruses from pigs in korea.due to dual susceptibility to both human and avian influenza a viruses, pigs are believed to be effective intermediate hosts for the spread and production of new viruses with pandemic potential. in early 2008, two swine h5n2 viruses were isolated from our routine swine surveillance in korea. the sequencing and phylogenetic analysis of surface proteins revealed that the sw/korea/c12/08 and sw/korea/c13/08 viruses were derived from avian influenza viruses of the eurasian lineage. however, although ...200919359528
development of a live-attenuated influenza b deltans1 intranasal vaccine candidate.we discovered a unique, single amino acid mutation in the influenza b m1 protein promoting viral growth of ns1 truncation mutants in vero cells. due to this mutation, we were able to generate an influenza b virus lacking the complete ns1 open reading frame (deltans1-b virus) by reverse genetics, which was growing to titers of 8log(10)tcid(50)/ml in a vero cell culture-based micro-carrier fermenter. the deltans1-b vaccine candidate was attenuated in ifn-competent hosts such as human alveolar epit ...200919366569
minimal molecular constraints for respiratory droplet transmission of an avian-human h9n2 influenza a virus.pandemic influenza requires interspecies transmission of an influenza virus with a novel hemagglutinin (ha) subtytpe that can adapt to its new host through either reassortment or point mutations and transmit by aerosolized respiratory droplets. two previous pandemics of 1957 and 1968 resulted from the reassortment of low pathogenic avian viruses and human subtypes of that period; however, conditions leading to a pandemic virus are still poorly understood. given the endemic situation of avian h9n ...200919380727
single- and multiple-clade influenza a h5n1 vaccines induce cross protection in ferrets.the rapid evolution, genetic diversity, broad host range, and increasing human infection with avian influenza a (h5n1) viruses highlight the need for an efficacious cross-clade vaccine. using the ferret model, we compared induction of cross-reactive immunity and protective efficacy of three single-clade h5n1 vaccines and a novel multiple-clade h5n1 vaccine, with and without mf59 adjuvant. reverse genetics (rg) was used to generate vaccine viruses containing the hemagglutinin (ha) and neuraminida ...200919406182
infection with human h1n1 influenza virus affects the expression of sialic acids of metaplastic mucous cells in the ferret airways.glycans terminating in sialic acids serve as receptors for influenza viruses. in this study ferrets were infected with influenza virus a/new caledonia/20/99, and the in situ localization of sialic acids linked alpha2-3 and alpha2-6 in the airways was investigated in infected and non-infected animals by use of sialic acid detecting lectins and a monoclonal antibody towards the sialyl-tn antigen. the goblet cells in the bronchi from non-infected ferrets expressed sialyl alpha 2-6gal glycans, while ...200919447147
evaluation of vaccines for h5n1 influenza virus in ferrets reveals the potential for protective single-shot immunization.as part of influenza pandemic preparedness, policy decisions need to be made about how best to utilize vaccines once they are manufactured. since h5n1 avian influenza virus has the potential to initiate the next human pandemic, isolates of this subtype have been used for the production and testing of prepandemic vaccines. clinical trials of such vaccines indicate that two injections of preparations containing adjuvant will be required to induce protective immunity. however, this is a working ass ...200919457991
lipid vesicle size of an oral influenza vaccine delivery vehicle influences the th1/th2 bias in the immune response and protection against infection.previous studies, using parenteral administration of antigen in lipid vesicles, have indicated a possible role for vesicle size in determining the th1/th2 bias of the resulting immune response. we have also demonstrated that the incorporation of bile salts into lipid vesicles (bilosomes) allows successful induction of mucosal and systemic immunity via the oral route. the following study was therefore carried out to determine whether size could also influence the th1/th2 bias in the immune respon ...200919464545
zoonotic potential of highly pathogenic avian h7n3 influenza viruses from pakistan.h5 and h7 avian influenza viruses can become highly pathogenic in chickens after interspecies transmission. these viruses have transmitted directly to humans from birds in eurasia and africa (h5n1), the netherlands (h7n7), and canada (h7n3). here we report antigenic, sequence, and phylogenetic analyses of h7n3 viruses isolated from chickens in pakistan from 1995 to 2002. we compared the pathogenic and zoonotic potential of the pakistani viruses in avian and mammalian hosts. in chickens, all of t ...200919535120
a trivalent virus-like particle vaccine elicits protective immune responses against seasonal influenza strains in mice and ferrets.there is need for improved human influenza vaccines, particularly for older adults who are at greatest risk for severe disease, as well as to address the continuous antigenic drift within circulating human subtypes of influenza virus. we have engineered an influenza virus-like particle (vlp) as a new generation vaccine candidate purified from the supernatants of sf9 insect cells following infection by recombinant baculoviruses to express three influenza virus proteins, hemagglutinin (ha), neuram ...200919554101
naturally occurring influenza infection in a ferret (mustela putorius furo) colony.tissue samples from 2 juvenile ferrets (mustela putorius furo) from a colony that was undergoing an outbreak of respiratory disease were submitted to the iowa state university veterinary diagnostic laboratory. microscopic examination of lung samples revealed bronchointerstitial pneumonia with necrotizing bronchiolitis. influenza a virus was detected in sections of formalin-fixed lung by immunohistochemistry and reverse transcription polymerase chain reaction assay. a field investigation of the p ...200919564504
fitness of pandemic h1n1 and seasonal influenza a viruses during co-infection: evidence of competitive advantage of pandemic h1n1 influenza versus seasonal influenza.on june 11, 2009 the world health organization (who) declared a new h1n1 influenza pandemic. this pandemic strain is as transmissible as seasonal h1n1 and h3n2 influenza a viruses. major concerns facing this pandemic are whether the new virus will replace, co-circulate and/or reassort with seasonal h1n1 and/or h3n2 human strains. using the ferret model, we investigated which of these three possibilities were most likely favored. our studies showed that the current pandemic virus is more transmis ...200920029606
[hemagglutination inhibition test for retrospective diagnosis of avian influenza in mammals].to compare usage of native and formalinized erythrocytes from different animal species in hemagglutination inhibition (hi) test for detection of level of specific antibodies to h5n1 influenza virus in sera of mammals.200920063797
efficient transmission of swine-adapted but not wholly avian influenza viruses among pigs and from pigs to ferrets.pigs are considered to be intermediate hosts for the transmission of avian influenza viruses (aivs) between birds and humans, but the transmissibility of aivs among pigs and from pigs to other mammals remains largely unexplored.200919919303
influenza b virus causes milder pathogenesis and weaker inflammatory responses in ferrets than influenza a virus.abstract it is unknown why the influenza b virus causes less severe clinical signs than the influenza a virus in humans. here we show that influenza b virus induces a lower levels of inflammatory cytokines in the lungs of infected ferrets, and causes less pathological damage to their lung tissues than does influenza a virus. the copy numbers of inflammatory cytokine genes, such as tnf-alpha and ifn-alpha, was significantly lower in the lungs of ferrets infected with influenza b virus than in tho ...200919951179
[study on evolutionary origin of influenza a virus (h1n1) based on ha gene].to determine the evolutionary rate and divergence time of influenza a virus ha gene isolated recently worldwide pandemic and explore the origin and its transmission.200919954063
das181 inhibits h5n1 influenza virus infection of human lung tissues.das181 is a novel candidate therapeutic agent against influenza virus which functions via the mechanism of removing the virus receptor, sialic acid (sia), from the adjacent glycan structures. das181 and its analogues have previously been shown to be potently active against multiple strains of seasonal and avian influenza virus strains in several experimental models, including cell lines, mice, and ferrets. here we demonstrate that das181 treatment leads to desialylation of both alpha2-6-linked a ...200919596886
zanamivir-resistant influenza viruses with a novel neuraminidase mutation.the neuraminidase inhibitors zanamivir and oseltamivir are marketed for the treatment and prophylaxis of influenza and have been stockpiled by many countries for use in a pandemic. although recent surveillance has identified a striking increase in the frequency of oseltamivir-resistant seasonal influenza a (h1n1) viruses in europe, the united states, oceania, and south africa, to date there have been no reports of significant zanamivir resistance among influenza a (h1n1) viruses or any other hum ...200919641000
in vitro and in vivo characterization of new swine-origin h1n1 influenza viruses.influenza a viruses cause recurrent outbreaks at local or global scale with potentially severe consequences for human health and the global economy. recently, a new strain of influenza a virus was detected that causes disease in and transmits among humans, probably owing to little or no pre-existing immunity to the new strain. on 11 june 2009 the world health organization declared that the infections caused by the new strain had reached pandemic proportion. characterized as an influenza a virus ...200919672242
partial direct contact transmission in ferrets of a mallard h7n3 influenza virus with typical avian-like receptor specificity.avian influenza viruses of the h7 subtype have caused multiple outbreaks in domestic poultry and represent a significant threat to public health due to their propensity to occasionally transmit directly from birds to humans. in order to better understand the cross species transmission potential of h7 viruses in nature, we performed biological and molecular characterizations of an h7n3 virus isolated from mallards in canada in 2001.200919682381
use of animal models to understand the pandemic potential of highly pathogenic avian influenza viruses.it has been 40 years since the last influenza pandemic and it is generally considered that another could occur at any time. recent introductions of influenza a viruses from avian sources into the human population have raised concerns that these viruses may be a source of a future pandemic strain. therefore, there is a need to better understand the pathogenicity of avian influenza viruses for mammalian species so that we may be better able to predict the pandemic potential of such viruses and dev ...200919695381
vaccination focusing immunity on conserved antigens protects mice and ferrets against virulent h1n1 and h5n1 influenza a viruses.immunization against conserved virus components induces broad, heterosubtypic protection against diverse influenza a viruses, providing a strategy for controlling unexpected outbreaks or pandemics until strain-matched vaccines become available. this study characterized immunization to nucleoprotein (np) and matrix 2 (m2) by dna priming followed by parenteral or mucosal boosting in mice and ferrets. dna vaccination followed by boosting with antigen-matched recombinant adenovirus (rad) or cold-ada ...200919729082
measurement of neutralizing antibody responses against h5n1 clades in immunized mice and ferrets using pseudotypes expressing influenza hemagglutinin and neuraminidase.neutralizing antibody is associated with the prevention and clearance of influenza virus infection. microneutralization (mn) and hemagglutination inhibition (hi) assays are currently used to evaluate neutralizing antibody responses against human and avian influenza viruses, including h5n1. the mn assay is somewhat labor intensive, while hi is a surrogate for neutralization. moreover, use of replication competent viruses in these assays requires biosafety level 3 (bsl-3) containment. therefore, a ...200919732860
an early 'classical' swine h1n1 influenza virus shows similar pathogenicity to the 1918 pandemic virus in ferrets and mice.the 1918 pandemic influenza virus has demonstrated significant pathogenicity in animal models and is the progenitor of 'classical' swine and modern seasonal human h1n1 lineages. here we characterize the pathogenicity of an early 'classical' swine h1n1 influenza a virus isolated in 1931 compared to the pathogenicity of the 1918 pandemic virus and a seasonal h1n1 virus in mice and ferrets. a/swine/iowa/31 (sw31) and the 1918 influenza viruses were uniformly lethal in mice at low doses and produced ...200919733889
recent human influenza a/h3n2 virus evolution driven by novel selection factors in addition to antigenic drift.examination of the evolutionary dynamics of complete influenza viral genomes reveals that other processes, in conjunction with antigenic drift, play important roles in viral evolution and selection, but there is little biological evidence to support these genomic data. previous work demonstrated that after the a/fujian/411/2002-like h3n2 influenza a epidemic during 2003-2004, a preexisting nondominant fujian-like viral clade gained a small number of changes in genes encoding the viral polymerase ...200919743921
aerosol transmission of influenza a virus: a review of new studies.over the past few years, prompted by pandemic preparedness initiatives, the debate over the modes of transmission of influenza has been rekindled and several reviews have appeared. arguments supporting an important role for aerosol transmission that were reviewed included prolonged survival of the virus in aerosol suspensions, demonstration of the low infectious dose required for aerosol transmission in human volunteers, and clinical and epidemiological observations were disentanglements of larg ...200919773292
the influence of the multi-basic cleavage site of the h5 hemagglutinin on the attenuation, immunogenicity and efficacy of a live attenuated influenza a h5n1 cold-adapted vaccine virus.a recombinant live attenuated influenza virus deltah5n1 vaccine with a modified hemagglutinin (ha) and intact neuraminidase genes from a/vietnam/1203/04 (h5n1) and six remaining genome segments from a/ann arbor/6/60 (h2n2) cold-adapted (aa ca) virus was previously shown to be attenuated in chickens, mice and ferrets. evaluation of the recombinant h5n1 viruses in mice indicated that three independent factors contributed to the attenuation of the deltah5n1 vaccine: the attenuating mutations specif ...200919833372
a miniaturized assay for influenza neuraminidase-inhibiting antibodies utilizing reverse genetics-derived antigens.antibodies to neuraminidase (na) contribute to protection during influenza virus infection, but na inhibition (ni) titers are not routinely analyzed in vaccine trials. one reason is the cumbersome nature of the conventional thiobarbituric acid (tba) ni assay, which uses chemical methods to quantify free sialic acid following incubation of na with substrate in the presence of serum. in addition, the assay is complicated by the need to use virus of a hemagglutinin (ha) subtype novel to the host to ...200921462400
development of a new candidate h5n1 avian influenza virus for pre-pandemic vaccine production.highly pathogenic h5n1 avian influenza viruses currently circulating in birds have caused hundreds of human infections, and pose a significant pandemic threat. vaccines are a major component of the public health preparedness for this likely event. the rapid evolution of h5n1 viruses has resulted in the emergence of multiple clades with distinct antigenic characteristics that require clade-specific vaccines. a variant h5n1 virus termed clade 2.3.4 emerged in 2005 and has caused multiple fatal inf ...200919903211
cloning, expression and immunoassay detection of ferret ifn-gamma.ferrets (mustela putorius furo) develop symptoms upon influenza infection that resemble those of humans, including sneezing, body temperature variation and weight loss. highly pathogenic strains of influenza a, such as h5n1, have the capacity to cause severe illness or death in ferrets. the use of ferrets as a model of influenza infection is currently limited by a lack of species-specific immunological reagents. interferon gamma (ifn-gamma) plays a key role in the development of innate and adapt ...200818262264
a plant-produced influenza subunit vaccine protects ferrets against virus challenge.influenza a viruses are of major concern for public health, causing worldwide epidemics associated with high morbidity and mortality. vaccines are critical for protection against influenza, but given the recent emergence of new strains with pandemic potential, and some limitations of the current production systems, there is a need for new approaches for vaccine development.200819453491
the pig as a mixing vessel for influenza viruses: human and veterinary implications.influenza a viruses are highly infectious respiratory pathogens that can infect many species. birds are the reservoir for all known influenza a subtypes; and novel influenza viruses can emerge from birds and infect mammalian species including humans. because swine are susceptible to infection with both avian and human influenza viruses, novel reassortant influenza viruses can be generated in this mammalian species by reassortment of influenza viral segments leading to the "mixing vessel" theory. ...200819565018
cross-protection against lethal h5n1 challenge in ferrets with an adjuvanted pandemic influenza vaccine.unprecedented spread between birds and mammals of highly pathogenic avian influenza viruses (hpai) of the h5n1 subtype has resulted in hundreds of human infections with a high fatality rate. this has highlighted the urgent need for the development of h5n1 vaccines that can be produced rapidly and in sufficient quantities. potential pandemic inactivated vaccines will ideally induce substantial intra-subtypic cross-protection in humans to warrant the option of use, either prior to or just after th ...200818167560
plasmid dna-based vaccines protect mice and ferrets against lethal challenge with a/vietnam/1203/04 (h5n1) influenza virus.plasmid dna (pdna) vaccines represent an alternative to conventional inactivated influenza vaccines that are likely to experience supply constraints during a pandemic. several vaxfectin-formulated pdna vaccines were tested in mice and ferrets for efficacy against a lethal challenge with the highly pathogenic a/vietnam/1203/04 (h5n1) influenza virus strain; the vaccines encoded influenza a virus hemagglutinin (ha), and/or nucleoprotein (np), and m2 protein. complete protection from death and dise ...200818513153
heterosubtypic protection against pathogenic human and avian influenza viruses via in vivo electroporation of synthetic consensus dna antigens.the persistent evolution of highly pathogenic avian influenza (hpai) highlights the need for novel vaccination techniques that can quickly and effectively respond to emerging viral threats. we evaluated the use of optimized consensus influenza antigens to provide broad protection against divergent strains of h5n1 influenza in three animal models of mice, ferrets, and non-human primates. we also evaluated the use of in vivo electroporation to deliver these vaccines to overcome the immunogenicity ...200818575608
a live attenuated cold-adapted influenza a h7n3 virus vaccine provides protection against homologous and heterologous h7 viruses in mice and ferrets.the appearance of human infections caused by avian influenza a h7 subtype viruses underscores their pandemic potential and the need to develop vaccines to protect humans from viruses of this subtype. a live attenuated h7n3 virus vaccine was generated by reverse genetics using the ha and na genes of a low pathogenicity a/chicken/bc/cn-6/04 (h7n3) virus and the six internal protein genes of the cold-adapted a/ann arbor/6/60 ca (h2n2) virus. the reassortant h7n3 bc 04 ca vaccine virus was temperatu ...200818585748
treatment of influenza a (h1n1) virus infections in mice and ferrets with cyanovirin-n.cyanovirin-n (cv-n), a protein derived from nostoc ellipsosporum, neutralizes influenza virus infectivity by binding to specific high-mannose oligosaccharides (oligomannose-8 and -9) at glycosylation sites on the viral hemagglutinin ha1 subunit. mouse-adapted viruses lose sensitivity to cv-n due to ha1 mutations that eliminate these glycosylation sites. recently we created a hybrid (reassortant) influenza a/wsn/33 (h1n1) virus containing the ha gene of a/new caledonia/20/99 (h1n1) with an asp225 ...200818601954
domestic pigs have low susceptibility to h5n1 highly pathogenic avian influenza viruses.genetic reassortment of h5n1 highly pathogenic avian influenza viruses (hpai) with currently circulating human influenza a strains is one possibility that could lead to efficient human-to-human transmissibility. domestic pigs which are susceptible to infection with both human and avian influenza a viruses are one of the natural hosts where such reassortment events could occur. virological, histological and serological features of h5n1 virus infection in pigs were characterized in this study. two ...200818617994
animal models in influenza vaccine testing.the threat of a pandemic outbreak of influenza a h5n1 and h2n2 has brought attention to the development of new vaccines. regulatory authorities require companies to provide data proving the effectiveness of vaccines, which cannot, however, be based on real efficacy data in humans. a weight-of-evidence approach may be used, based on evidence of protection in an appropriate animal model and the satisfaction of the surrogate end points in the clinical situation. in this review, we will discuss vari ...200818665776
oseltamivir-resistant influenza a viruses are transmitted efficiently among guinea pigs by direct contact but not by aerosol.influenza viruses resistant to the neuraminidase (na) inhibitor oseltamivir arise under drug selection pressure both in vitro and in vivo. several mutations in the active site of the viral na are known to confer relative resistance to oseltamivir, and influenza viruses with certain oseltamivir resistance mutations have been shown to transmit efficiently among cocaged ferrets. however, it is not known whether na mutations alter aerosol transmission of drug-resistant influenza virus. here, we demo ...200818684820
Refresh
firstprev
123456
nextlast
Displaying items 301 - 400 of 593