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adjuvant effect of cliptox on the protective immune response induced by an inactivated vaccine against foot and mouth disease virus in mice.foot and mouth disease (fmd) is an acute disease caused by foot and mouth disease virus (fmdv) which causes important economy losses, this is why it is necessary to obtain a vaccine that stimulates a rapid and long-lasting protective immune response. cliptox is a mineral microparticle that in earlier studies has shown adjuvant activity against different antigens. in this study we have examined the effects of cliptox on the magnitude and type of immunity elicited in response to inactivated fmdv ( ...201020637310
high-resolution in vivo imaging of breast cancer by targeting the pro-invasive integrin alphavbeta6.the integrin alphavbeta6 is expressed only on epithelia and then usually only during processes of tissue remodelling including cancer, where its high expression correlates with reduced survival. thus, alphavbeta6 represents an important target for imaging and therapy of cancer and new molecular-specific targeting agents are required. we have developed a20fmdv2, a peptide derived from the vp1 coat protein of foot-and-mouth-disease virus that binds specifically and stably to alphavbeta6. using a n ...201020629113
molecular characterization of foot-and-mouth disease viruses collected from sudan.the aim of this study was to characterize foot-and-mouth disease (fmd) viruses collected between 2004 and 2008 from sudan, a country where fmd is endemic. using virus isolation and antigen elisa, three fmd virus serotypes (o, a and sat2) were detected in 24 samples that were submitted to the fao world reference laboratory for fmd. pan-serotypic real-time rt-pcr assays targeting the 5' untranslated region (5'utr) and 3d genes of fmd virus were also used to contribute to the laboratory diagnosis o ...201020626708
diversity and transboundary mobility of serotype o foot-and-mouth disease virus in east africa: implications for vaccination policies.foot-and-mouth disease (fmd) virus serotype o has been responsible for most reported outbreaks of the disease in east africa. a sustained campaign for the past 40 years to control fmd mainly by vaccination, combined with quarantine and zoosanitary measures has been undertaken with limited success. we investigated the genetic relationships among serotype o strains in eastern africa using complete vp1 coding region sequences obtained from 46 fmd virus isolates collected in kenya in the years 1964- ...201020619358
[prokaryotic expression, protein purification and reactivity analysis of the vp1 and its c terminus of a south african isolate of fmdv serotype sat2].to induce the expression of structure protein vp1 and its c terminus of foot-and-mouth disease virus (fmdv) serotype sat2 in e.coli and analyze their reactivities with fmdv positive antiserum.201020619084
co-circulation of two extremely divergent serotype sat 2 lineages in kenya highlights challenges to foot-and-mouth disease control.amongst the sat serotypes of foot-and-mouth disease virus (fmdv), the sat 2 serotype is the most widely distributed throughout sub-saharan africa. kenyan serotype sat 2 viruses have been reported to display the highest genetic diversity for the serotype globally. this complicates diagnosis and control, and it is essential that patterns of virus circulation are known in order to overcome these difficulties. this study was undertaken to establish patterns of evolution of fmdv serotype sat 2 in ken ...201020614146
a recombinant humanized monoclonal antibody completely protects mice against lethal challenge with venezuelan equine encephalitis virus.a recombinant humanized antibody to venezuelan equine encephalitis virus (veev) was constructed in a monocistronic adenoviral expression vector with a foot-and-mouth-disease virus-derived 2a self-cleavage oligopeptide inserted between the antibody heavy and light chains. after expression in mammalian cells, the heavy and light chains of the humanized antibody (hu1a4a1igg1-2a) were completely cleaved and properly dimerized. the purified hu1a4a1igg1-2a retained veev binding affinity and neutralizi ...201020600509
foot-and-mouth disease virus replicates only transiently in well-differentiated porcine nasal epithelial cells.three-dimensional (3d) porcine nasal mucosal and tracheal mucosal epithelial cell cultures were developed to analyze foot-and-mouth disease virus (fmdv) interactions with mucosal epithelial cells. the cells in these cultures differentiated and polarized until they closely resemble the epithelial layers seen in vivo. fmdv infected these cultures predominantly from the apical side, primarily by binding to integrin alphav beta6, in an arg-gly-asp (rgd)-dependent manner. however, fmdv replicated onl ...201020592089
the early pathogenesis of foot-and-mouth disease in cattle after aerosol inoculation. identification of the nasopharynx as the primary site of infection.to characterize the early events of foot-and-mouth disease virus (fmdv) infection in cattle subsequent to simulated natural exposure, 16 steers were aerosol inoculated with fmdv and euthanized at various times. samples were collected from each steer antemortem (serum, nasal swabs, and oral swabs) and postmortem (up to 40 tissues per animal) and screened for fmdv by virus isolation and for fmdv rna by real-time reverse transcription polymerase chain reaction. tissues that tested positive for fmdv ...201020587691
baculovirus treatment fully protects mice against a lethal challenge of fmdv.foot-and-mouth disease virus (fmdv) causes a highly contagious and economically devastating disease that affects cattle, swine, goat and sheep among others. fmdv is able to overcome the initial host innate immune response by inhibiting the induction of antiviral molecules at both the transcriptional and the translational levels. it has been demonstrated that fmdv a/arg/2001 causes the death of adult c57bl/6 mice within 72h. we evaluated the capacity of autographa californica nuclear polyhedrosis ...201020580746
domain disruptions of individual 3b proteins of foot-and-mouth disease virus do not alter growth in cell culture or virulence in cattle.picornavirus rna replication is initiated by a small viral protein primer, 3b (also known as vpg), that is covalently linked to the 5' terminus of the viral genome. in contrast to other picornaviruses that encode a single copy of 3b, foot-and-mouth disease virus (fmdv) encodes three copies of 3b. viruses containing disrupted native sequence or deletion of one of their three 3b proteins were derived from a fmdv a24 cruzeiro full-length cdna infectious clone. mutant viruses had growth characterist ...201020580394
a simulation model for the potential spread of foot-and-mouth disease in the castile and leon region of spain.a spatial stochastic model was used to simulate the spread of a foot-and-mouth disease (fmd) epidemic in the castile-and-leon (cyl) region of spain. the model was fitted using information available on premises demographics and on assumptions for animal movements, indirect contacts, and airborne exposure. control measures dictated by spanish and european union regulations constituted a reference strategy to which six alternative control strategies were compared. for the reference strategy, the me ...201020579754
[fusion expression of asia i type fmdv neutralizing epitope with heavy chain constant region of sheep igg and the assessment of its immunogenicity].vp1 is a major antigenic protein of foot-and-mouth disease virus(fmdv), which induces the immune response against fmdv infection, and contains several epitopes of the virus. we designed and chemically synthesized a dna fragment which encoding a tandem repeat protein of 136-160aa and 198-211aa of a strain of type asia i fmdv, and cloned the gene of heavy chain constant region of sheep igg. by using the bamh i, ecor i and xho i sites, both genes were cloned into pproexhtb vector in turn to form a ...201020575432
status of foot-and-mouth disease in pakistan.the present study reports the distribution of different serotypes of foot-and-mouth disease virus (fmdv) in pakistan during the period 1952-2007. during this time, a total of 1,543 epithelial samples out of 2,484 tested were found positive for various serotypes of fmdv. serotype o was found to be the most prevalent (p < 0.001) followed by serotype asia-1 and a. serotype c was detected only in 1954, 1963 and 1995. the disease was found to be more prevalent (p < 0.0001) in cattle than buffaloes. t ...201020571838
qualitative assessment of the commodity risk for spread of foot-and-mouth disease associated with international trade in deboned beef.the risk of importing foot-and-mouth disease virus (fmdv) restricts trade in livestock and their products from parts of the world where the virus is present. this reduces trade opportunities and investment in the livestock sector of many developing countries and constrains global food supply. this review focuses on the risks associated with trade in deboned beef (db) from foot-and-mouth disease (fmd)-infected cattle, countries or zones. a definition of db is provided along with a description of ...201020569417
letter to the editor. loss of plasmacytoid dendritic cell function coincides with lymphopenia and viremia during foot-and-mouth disease virus infection. 201020565298
multiple shrnas driven by u6 and cmv promoter enhances efficiency of antiviral effects against foot-and-mouth disease virus.foot-and-mouth disease (fmd) is an economically significant animal disease because of the speed of its transmission. the current vaccine for fmd provides no protection until 7 days post-vaccination, thus reducing its effectiveness in the case of an outbreak. small interfering rna (sirna) is a promising antiviral approach because it can induce a protective response much more rapidly. this study is the first report to apply multiple short hairpin rna (shrna) expression systems to inhibit foot-and- ...201020561543
antibodies against foot-and-mouth disease (fmd) virus in african buffalos (syncerus caffer) in selected national parks in uganda (2001-2003).in east africa, the foot-and-mouth disease (fmd) virus (fmdv) isolates have over time included serotypes o, a, c, southern african territories (sat) 1 and sat 2, mainly from livestock. sat 3 has only been isolated in a few cases and only in african buffalos (syncerus caffer). to investigate the presence of antibodies against fmdv serotypes in wildlife in uganda, serological studies were performed on buffalo serum samples collected between 2001 and 2003. thirty-eight samples from african buffalos ...201020561289
difference in the level of interferon gamma mrna transcripts on stimulation of cattle and buffalo mononuclear cells with foot and mouth disease virus-antigen: a possible role of sequence variation in promoter region.in an attempt to resolve the claim that buffaloes differ from cattle in disease progression, this study was undertaken to compare the mitogen (cona) or antigen (foot and mouth disease virus) induced expression levels of interferon gamma (ifn-γ mrna in peripheral blood mononuclear cells (pbmcs) by real-time quantitative pcr. in general, the levels of ifn-γ mrna were lower in buffaloes than in crossbred cattle. significantly higher levels of ifn-γ mrna were also observed in crossbred cattle when i ...201120541234
chitosan can stop or postpone the death of the suckling mice challenged with foot-and-mouth disease virus.in the study, a method called "hardening in liquid phase" for preparing chitosan granules with glutaraldehyde as crosslinker and tween 80 as surfactant and paraffin liquid as dispersant was established. the chitosan granules were light yellow and insoluble in water or oil, but they swelled in acid solution and narrowed in neutral or alkaline solution. furthermore, some of characteristics of the chitosan granules were revealed. (a) stability: their shapes were stable at ph 7.0 and ph 8.0 and -30 ...201020540780
foot and mouth disease in animals in sharkia governorate - egypt.this study was carried out to determine the current state of foot and mouth disease (fmd) in different animal species in sharkia governorate in egypt. in addition, we investigated the spreading of the virus through water and soil in the animal environment as well as by rodents. the isolation rates of fmd virus in tissue culture were 39.6%, 11.4%, 41.2% and 100% for cattle, buffalo, sheep and goat respectively. all animals did not show any clinical signs for fmd. in addition, the virus was isolat ...201020537095
functional expression of secreted proteins from a bicistronic retroviral cassette based on foot-and-mouth disease virus 2a can be position dependent.the expression of two or more genes from a single viral vector has been widely used to label or select for cells containing the transgenic element. identification of the foot-and-mouth disease virus (fmdv) 2a cleavage peptide as a polycistronic linker capable of producing equivalent levels of transgene expression has greatly improved this approach in the field of gene therapy. however, as a consequence of 2a posttranslational cleavage the upstream protein is left with a residual 19 amino acids f ...201020528679
the efficacy of fmd vaccine reduced non-structural proteins with a mab against 3b protein.a monoclonal antibody, 3bigg, against the prokaryotically expressed foot-and-mouth disease virus (fmdv) non-structural protein (nsp) 3b was obtained. the 3bigg-sepharose conjugant (3bmab-6bff) was prepared by adding the purified 3bigg into epoxy-activated sepharose 6bff, incubating with the inactivated fmdv, and then removing the sepharose by centrifugation. the vaccine was made from the supernatant emulsified with oil-adjuvant isa206. ten guinea pigs, 26 pigs and six cattle were vaccinated, and ...201020512625
foot and mouth disease: a story of resilience. 200920509460
effect of fmd vaccination on semen quality parameters in karan fries and murrah buffalo bulls.effect of foot and mouth disease (fmd) vaccination was studied on semen quality parameters of 19 karan fries (kf) and eight murrah (mu) breeding bulls during the period 2002 to 2004 at artificial breeding complex, ndri, karnal. a total of non-vaccinated 155 kf and 72 mu bulls' ejaculates were taken as control, while 169 kf and 51 mu bulls' ejaculates, collected after vaccination, were used to study the effect of vaccination stress. the results showed that fmd vaccination had no significant (p > ...201020509049
foot-and-mouth disease virus 2c is a hexameric aaa+ protein with a coordinated atp hydrolysis mechanism.foot-and-mouth disease virus (fmdv), a positive sense, single-stranded rna virus, causes a highly contagious disease in cloven-hoofed livestock. like other picornaviruses, fmdv has a conserved 2c protein assigned to the superfamily 3 helicases a group of aaa+ atpases that has a predicted n-terminal membrane-binding amphipathic helix attached to the main atpase domain. in infected cells, 2c is involved in the formation of membrane vesicles, where it co-localizes with viral rna replication complex ...201020507978
deletion mutants of vpg reveal new cytopathology determinants in a picornavirus.success of a viral infection requires that each infected cell delivers a sufficient number of infectious particles to allow new rounds of infection. in picornaviruses, viral replication is initiated by the viral polymerase and a viral-coded protein, termed vpg, that primes rna synthesis. foot-and-mouth disease virus (fmdv) is exceptional among picornaviruses in that its genome encodes 3 copies of vpg. why fmdv encodes three vpgs is unknown.201020505767
remaining vigilant for foot-and-mouth disease. 201020495175
differential gene expression in bovine cells infected with wild type and leaderless foot-and-mouth disease virus.the leader proteinase (l(pro)) of foot-and-mouth disease virus (fmdv) plays a critical role in viral pathogenesis. molecular studies have demonstrated that l(pro) inhibits translation of host capped mrnas and transcription of some genes involved in the innate immune response. we have used microarray technology to study the gene expression profile of bovine cells infected with wild type (wt) or leaderless fmdv. thirty nine out of approximately 22,000 bovine genes were selectively up-regulated by ...201020494391
heterogeneity and genetic variations of serotypes o and asia 1 foot-and-mouth disease viruses isolated in vietnam.six field foot-and-mouth disease viruses (fmdvs), including four serotype o and two serotype asia 1 strains, were collected from endemic outbreaks in 2005, 2006, and 2007 from four different provinces in vietnam. the viruses were isolated and genetically characterized for their complete genomic sequences. the genetic analysis based on the complete genomic coding sequences revealed that the four serotype o fmdvs were related to each other, sharing 95.2% nucleotide (nt) identity and 97.5-97.6% ami ...201020478669
localisation of theiler's murine encephalomyelitis virus protein 2c to the golgi apparatus using antibodies generated against a peptide region.the picornavirus 2c protein is highly conserved and indispensible for virus replication. polyclonal antibodies against theiler's murine encephalomyelitis virus (tmev) 2c protein were generated by immunisation of rabbits with a peptide comprising amino acids 31-210 of the protein. antibodies were used to investigate the localisation of 2c in infected cells by indirect immunofluorescence and confocal microscopy. analysis of infected cells revealed that the distribution of 2c changed during infecti ...201020471424
formation of virus-like particles from o-type foot-and-mouth disease virus in insect cells using codon-optimized synthetic genes.a recombinant baculovirus was constructed to simultaneously express codon-optimized virus-like particles (vlp), a vp1-2a-vp3 and vp0 of serotype o foot-and-mouth disease virus (fmdv), from individual promoters. the target proteins were expressed in insect cells at high level, as shown by indirect sandwich elisa; and the expressed vp1-2a-vp3 could autocatalytically be cleaved into the individual proteins, vp1-2a and vp3, as shown by western-blot analyses. in addition, in the insect cells, the str ...201020464450
evaluation of infectivity and transmission of different asian foot-and-mouth disease viruses in swine.most isolates of foot-and-mouth disease virus (fmdv) display a broad host range. since the late 1990s, the genetic lineage of panasia topotype fmdv serotype o has caused epidemics in the far east, africa, the united kingdom, france, the netherlands, and numerous other countries throughout europe and asia. in contrast, there are several fmdv isolates that exhibit a more restricted host range. a cathay topotype isolate of fmdv serotype o from the 1997 epizootic in taiwan (o/taw/97) demonstrated re ...201020458154
new vaccine design based on defective genomes that combines features of attenuated and inactivated vaccines.new vaccine designs are needed to control diseases associated with antigenically variable rna viruses. foot-and-mouth disease (fmd) is a highly contagious disease of livestock that inflicts severe economic losses. although the current whole-virus chemically inactivated vaccine has proven effective, it has led to new outbreaks of fmd because of incomplete inactivation of the virus or the escape of infectious virus from vaccine production premises. we have previously shown that serial passages of ...201020454676
development of a peptide-based immunochromatographic strip for differentiation of serotype o foot-and-mouth disease virus-infected pigs from vaccinated pigs.an immunochromatographic strip for discriminating foot-and-mouth disease virus (fmdv) infected from vaccinated pigs was developed based on synthetic peptide. five peptides designed from the amino acid sequences of nonstructural proteins (nsp) of fmdv were synthesized, and pep5 located in nsp 3b reacted strongly with serum from fmdv-infected pigs but did not react with serum samples from healthy vaccinated pigs. an immunochromatographic strip was developed by using colloidal gold labeled with pep ...201020453216
construction of a multiple targeting rnai plasmid that inhibits target gene expression and fmdv replication in bhk-21 cells and suckling mice.foot-and-mouth disease (fmd) is a highly contagious disease that afflicts cloven-hoofed animals. the etiological agent of fmd is foot-and-mouth disease virus (fmdv). the vp1 gene of fmdv is essential during the life cycle of the virus and plays a key role in the attachment of the virus to susceptible cells. we constructed a plasmid, pcwn11, that expresses sirnas multiple-targeting the vp1 genes of fmdv. we evaluated the gene silencing efficiency of the plasmid using an enhanced green fluorescent ...201020446035
increasing a robust antigen-specific cytotoxic t lymphocyte response by fmdv dna vaccination with il-9 expressing construct.various chemokines and cytokines as adjuvants can be used to improve efficacy of dna vaccination. in this study, we sought to investigate if a dna construct expressing il-9 (designed as prov-il9) as a molecular adjuvant enhance antigen specific immune responses elicited by the pcd-vp1 dna vaccination. mice immunized with pcd-vp1 combined with prov-il9 developed a strong humoral response. in addition, the coinoculation induced significant higher level of antigen-specific cell proliferation and cy ...201020445754
cell density-dependent expression of viral antigens during persistence of foot-and-mouth disease virus in cell culture.immunofluorescence analyses of fmdv persistently infected bhk-21 cells showed that in cultures from early stages of the persistence (passage 15) only about 10% of cells displayed viral antigens, while at late stages (passage 100) no fmdv antigen-positive cells were found. positive cells at passage 15 displayed a number of structural alterations that did not differ from those observed in lytically infected cells. in these monolayers, and remarkably, clusters of cells that exceeded confluence were ...201020444479
nmr solution structure of poliovirus uridylyated peptide linked to the genome (vpgpu).picornaviruses have a 22-24 amino acid peptide, vpg, bound covalently at the 5' end of their rna, that is essential for replication. vpgs are uridylylated at a conserved tyrosine to form vpgpu, the primer of rna synthesis by the viral polymerase. this first complete structure for any uridylylated vpg, of poliovirus type 1 (pv1)-vpgpu, shows that conserved amino acids in vpg stabilize the bound ump, with the uridine atoms involved in base pairing and chain elongation projected outward. comparing ...201020441784
molecular characterization and expression analysis of porcine integrins alphavbeta3, alphavbeta6 and alphavbeta8 that are potentially involved in fmdv infection.in the present study, we report the sequences and characterization of the porcine integrin cdnas encoding alphav, beta3, beta6 and beta8 subunits and compare them to those of other species. the coding sequences for the porcine alphav, beta3, beta6 and beta8 subunits were found to be 3141, 2289, 2367 and 2304 nucleotides in length, encoding 1046, 762, 788 and 767-amino-acid-residue protein, respectively. the porcine integrin alphav, beta3, beta6 and beta8 subunit shares common structural and func ...201020438833
recent spread of foot-and-mouth disease in the far east. 201020435988
pan-serotypic detection of foot-and-mouth disease virus by rt linear-after-the-exponential pcr.a reverse transcription linear-after-the-exponential polymerase chain reaction (rt late-pcr) assay was evaluated for detection of foot-and-mouth disease virus (fmdv). this pan-serotypic assay targets highly conserved sequences within the 3d (rna polymerase) region of the fmdv genome, and uses end-point hybridisation analysis of a single mismatch-tolerant low temperature probe to confirm the identity of the amplicons. an armored rna served as an internal control to validate virus negative results ...201020433917
crystal structure of equine rhinitis a virus in complex with its sialic acid receptor.equine rhinitis a virus (erav) shares many features with foot-and-mouth disease virus (fmdv) and both are classified within the genus aphthovirus of the family picornaviridae. erav is used as a surrogate for fmdv research as it does not require high-level biosecurity. in contrast to fmdv, which uses integrins as cellular receptors, the receptor for erav has been reported to involve the sugar moiety sialic acid. this study confirmed the importance of sialic acid for cell entry by erav and reports ...201020427563
analysis of synonymous codon usage in foot-and-mouth disease virus.in this study, we calculate the relative synonymous codon usage (rscu) values and codon usage bias (cub) values to carry out a comparative analysis of codon usage pattern for open reading frames (orfs) among 85 samples which belong to all seven serotypes of foot-and-mouth disease virus (fmdv). although the degree of cub for orfs is a relatively slight, there is a significant variation for cub among different serotypes, which is mainly determined by codon usage pattern depending on rscu. by compa ...201020425142
no between-pen transmission of foot-and-mouth disease virus in vaccinated pigs.many studies have shown transmission of foot-and-mouth disease virus (fmdv) within groups of pigs, even when vaccinated, but only limited information is available on transmission between pens. three new experiments were carried out in two replicates, which consisted of infectious pigs housed in a central pen surrounded by four separate pens. first, all pigs were non-vaccinated and pens were separated by a walkway of 40-70 cm. second, all pigs were non-vaccinated again but pens were adjacent. thi ...201020416264
assessment of gold nanoparticles as a size-dependent vaccine carrier for enhancing the antibody response against synthetic foot-and-mouth disease virus peptide.to assess the ability of gold nanoparticles (gnps) to act as a size-dependent carrier, a synthetic peptide resembling foot-and-mouth disease virus (fmdv) protein was conjugated to gnps ranging from 2 to 50 nm in diameter (2, 5, 8, 12, 17, 37, and 50 nm). an extra cysteine was added to the c-terminus of the fmdv peptide (pfmdv) to ensure maximal conjugation to the gnps, which have a high affinity for sulfhydryl groups. the resultant pfmdv-gnp conjugates were then injected into balb/c mice. immuni ...201020400818
characteristics of codon usage bias in two regions downstream of the initiation codons of foot-and-mouth disease virus.the mechanism of utilization of alternative two augs in foot-and-mouth disease virus (fmdv) is still unknown to date. in this study, the characteristics of codon usage bias (cub) of the region between the two augs (the region-la) and of the same-sized region behind the second aug (the region-lb) in 94 different fmdv rna sequences were analyzed using relative synonymous codon usage (rscu) values. the results indicated that many codons with negative cub were preferentially used in the region-la. t ...201020398725
structure of foot-and-mouth disease virus mutant polymerases with reduced sensitivity to ribavirin.passage of poliovirus (pv) or foot-and-mouth disease virus (fmdv) in the presence of ribavirin selected for viruses with decreased sensitivity to r, which included different mutations in their polymerase (3d): g64s located in the finger subdomain in the case of pv and m296i located within loop beta9-alpha11 at the active site in the case of fmdv. to investigate why disparate substitutions were selected in two closely related 3ds, we constructed fmdvs with a 3d that included either g62s (the equi ...201020392853
cell entry of the aphthovirus equine rhinitis a virus is dependent on endosome acidification.equine rhinitis a virus (erav) is genetically closely related to foot-and-mouth disease virus (fmdv), and both are now classified within the genus aphthovirus of the family picornaviridae. for disease security reasons, fmdv can be handled only in high-containment facilities, but these constraints do not apply to erav, making it an attractive alternative for the study of aphthovirus biology. here, we show, using immunofluorescence, pharmacological agents, and dominant negative inhibitors, that er ...201020375159
genetic and antigenic characterization of foot-and-mouth disease viruses isolated in taiwan between 1998 and 2009.a devastating outbreak of foot-and-mouth disease (fmd), caused by a porcinophilic serotype o virus, occurred in taiwan in march 1997. this outbreak was brought under control by means of a stamping-out policy and vaccination. although mandatory vaccination was conducted in taiwan between 1997 and 2007, sporadic outbreaks of fmd occurred between 1998 and 2009; however, the viruses that caused these outbreaks remain uncharacterized. this article reports the genetic and antigenic characterization of ...201020362404
degradation of foot-and-mouth disease virus during composting of infected pig carcasses.the objective of this study was to investigate the inactivation and degradation of foot-and-mouth disease (fmd) virus during composting of infected pig carcasses as measured by virus isolation in tissue culture and by real-time reverse transcriptase polymerase chain reaction (rrt-pcr). three fmd-infected pig carcasses were composted in a mixture of chicken manure and wood shavings in a biocontainment level 3 facility. compost temperatures had reached 50 degrees c and 70 degrees c by days 10 and ...201020357957
foot-and-mouth disease: the question of implementing vaccinal control during an epidemic.the question of whether or not to use vaccines during an epidemic of foot-and-mouth disease (fmd) has interested veterinary administrators for many decades. this review assesses the historical uses, successes and failures of vaccinal control, and addresses the questions of where, how, and when to use vaccination against fmd. approaching the problem in this manner can aid in identifying which tools are likely to be most effective during an epidemic, and how successful a given contingency plan mig ...201120350828
low diversity of foot-and-mouth disease serotype c virus in kenya: evidence for probable vaccine strain re-introductions in the field.most viruses are maintained by complex processes of evolution that enable them to survive but also complicate efforts to achieve their control. in this paper, we study patterns of evolution in foot-and-mouth disease (fmd) serotype c virus isolates from kenya, one of the few places in the world where serotype c has been endemic and is suspected to remain. the nucleotide sequences encoding the capsid protein vp1 from eight isolates collected between 1967 and 2004 were analysed for patterns of sequ ...201120334728
effect of foot-and-mouth disease virus capsid precursor protein and 3c protease expression on bovine herpesvirus 1 replication.several reports have previously shown that expression of the foot-and-mouth disease virus (fmdv) capsid precursor protein encoding region p1-2a together with the 3c protease (p1-2a/3c) results in correct processing of the capsid precursor into vp0, vp1 and vp3 and formation of fmdv capsid structures that are able to induce a protective immune response against fmdv challenge after immunization using naked dna constructs or recombinant viruses. to elucidate whether bovine herpesvirus 1 (bhv-1) mig ...201020333533
development of tobacco necrosis virus a as a vector for efficient and stable expression of fmdv vp1 peptides.plant virus-based expression systems provide attractive alternatives for production of animal virus-originated antigenic peptides. in the present study, an infectious cdna clone of tobacco necrosis virus a chinese isolate (tnv-a(c)) was used for expression of different peptides derived from foot and mouth disease virus (fmdv) serotype o vp1 fused downstream of the coat protein (cp) open reading frame (orf). chenopodium amaranticolor inoculated with in vitro transcripts of the chimaeras developed ...201020331532
[transmission risk for foot-and-mouth-disease in an animal-densed region in germany--results from an expert survey].due to its strong impact on economics and trading the foot-and-mouth-disease (fmd) is one of the most important animal diseases within animal husbandry. because no recent specific field observation for fmd exists in germany, the risk assessment needs validated epidemiological models to prepare decision tools for fmd-outbreak management. the aim of this investigation was therefore to prepare a risk assessment for different transmission pathways to use for fmd-models in future. to prepare a fmd-tr ...201020329640
an indirect elisa for serodiagnosis of cattle footrot caused by fusobacterium necrophorum.a serodiagnostic elisa (rl-elisa) using recombinant truncated leukotoxin protein pl2 (aa 311-644) of fusobacterium necrophorum as antigen was developed for detection of antibodies against f. necrophorum from cattle footrot. in rl-elisa, the recombinant diagnostic antigen showed no cross-reaction with antisera against bovine foot and mouth disease virus, bovine rhinotracheitis virus, bovine viral diarrhea virus, bovine rotavirus type a, bovine escherichia coli, and bovine salmonella. the rl-elisa ...201020304080
genetic characterization of indian type o fmd virus 3a region in context with host cell preference.the 3a region of foot-and-mouth disease virus has been implicated in host range and virulence. for example, amino acid deletions in the porcinophilic strain (o/taw/97) at 93-102aa of the 153 codons long 3a protein have been recognized as the determinant of species specificity. in the present study, 18 type o fmdv isolates from india were adapted in different cell culture systems and the 3a sequence was analyzed. these isolates had complete 3a coding sequence (153aa) and did not exhibit growth re ...201020302973
screwworms, cochliomyia hominivorax, reared for mass release do not carry and spread foot-and-mouth disease virus and classical swine fever virus.experiments were done to determine if transporting live screwworms cochliomyia hominivorax coquerel (diptera: calliphoridae) for developing new strains from countries where foot-and-mouth disease and classical swine fever are endemic, to the mass rearing facilities in mexico and panama, may introduce these exotic diseases into these countries. are screwworms capable of harboring and spreading foot-and-mouth disease virus (fmdv) and classical swine fever virus (csfv) when they are grown in virus- ...200820302530
typing of the virus of foot-and-mouth disease. 194720266311
[not available]. 194720244009
[not available]. 194720244008
[rescue of bovine asia 1 serotype foot-and-mouth disease virus from a full-length cdna clone].after sequencing the asia 1 foot-and-mouth disease virus (fmdv) (as01 strain), we amplified the two fragments covering the whole genome by overlapping pcr and long pcr. the 5' fragment was 1.8 kb in length including 15cs, and the 3' fragment was 6.7 kb in length. the two fragments were cloned into the pbluescript sk vector to construct recombinant plasmid pbsas carrying the full-length cdna of fmdv as01 strain. the rna transcript was synthesized in vitro using t7 polymerase and transfected into ...200920222458
[morphological observation of bovine kidney (mdbk) cells effected by foot-and-mouth disease virus l(pro)].in order to explore the morphological changes of bovine kidney (mdbk) cells induced by foot-and-mouth disease virus (fmdv) l protease, we induced the expression of fmdv l protease in bovine kidney cells (mdbk) artificially. all work is carried out on the basis of a stable mdbk cell line inducibly expresses the lab gene under the control of tetracycline. we use cell morphology, hoechst 33258 staining, ao-eb staining, and dna ladder abstraction to research the morphological changes of mdbk cells. ...200920222457
characterization of foot-and-mouth disease virus antigen by surface-enhanced laser desorption ionization-time of flight-mass spectrometry in aqueous and oil-emulsion formulations.we have used a novel method, surface-enhanced laser desorption ionization-time of flight-mass spectrometry (seldi-tof-ms), to characterize foot-and-mouth disease virus (fmdv) vaccine antigens. using specific capture with fmdv binding recombinant antibody fragments and tryptic digestion of fmdv antigens the spectral peaks representing the fmdv structural proteins vp1, vp2, vp3 and vp4 were identified. vp1 existed as 2 variants differing by 0.2kda and vp4 as 8 variants differing by 14-17da. such h ...201020206283
parameterization of the duration of infection stages of serotype o foot-and-mouth disease virus: an analytical review and meta-analysis with application to simulation models.foot-and-mouth disease (fmd) is considered one of the most important infectious diseases of livestock because of the devastating economic consequences that it inflicts in affected regions. the value of critical parameters, such as the duration of the latency or the duration of the infectious periods, which affect the transmission rate of the fmd virus (fmdv), are believed to be influenced by characteristics of the host and the virus. disease control and surveillance strategies, as well as fmd si ...201020205988
the development of oral fluid-based diagnostics and applications in veterinary medicine.the purpose of this review was to discuss the history of the development and implementation of oral fluid diagnostics for infectious diseases of humans and domestic animals. the use of oral fluid for the assessment of health and diagnosis of disease in humans and animals has a surprisingly long history. as early as 1909, pollaci and ceraulo reported sensitive and specific agglutination of 'micrococcus melitensis' (brucella melitensis) by oral fluid from patients diagnosed with malta fever. a 198 ...201020202287
marker vaccine potential of a foot-and-mouth disease virus with a partial vp1 g-h loop deletion.previous work in cattle and pigs demonstrated that protection against foot-and-mouth disease (fmd) could be achieved following vaccination with chimeric foot-and-mouth disease virus (fmdv) vaccines, in which the vp1 g-h loop had been substituted with that from another serotype. this indicated that the vp1 g-h loop may not be essential for the protection of natural hosts against fmdv. if this could be substantiated there would be potential to develop fmd marker vaccines, characterised by the abse ...201020199761
a recombinant truncated fmdv 3ab protein used to better distinguish between infected and vaccinated cattle.to distinguish the antibodies induced by foot-and-mouth disease virus (fmdv) infection from those induced by vaccination, a recombinant n-terminal truncated fmdv non-structural protein (nsp) of 3ab, designated as r3ab, was constructed by deleting 80 amino acids displayed about 30% homology to transposase is4 family protein of escherichia coli, expressed in e. coli bl21 (de3) and then purified. the r3ab was majorly expressed in soluble fraction and presented as homogeneous monomers after purifica ...201020197135
tailoring the switch from ires-dependent to 5'-end-dependent translation with the rnase p ribozyme.translation initiation driven by internal ribosome entry site (ires) elements is dependent on the structural organization of the ires region. we have previously shown that a structural motif within the foot-and-mouth-disease virus ires is recognized in vitro as substrate for the synechocystis sp. rnase p ribozyme. here we show that this structure-dependent endonuclease recognizes the ires element in cultured cells, leading to inhibition of translation. inhibition of ires activity was dependent o ...201020194518
the relationship between cellular immune response to foot-and-mouth disease virus asia 1 and viral persistence in indian cattle (bosindicus).foot-and-mouth disease (fmd), the most contagious animal disease, is associated with persistent viral infection in ruminants, despite the induction of systemic immune response. the present study was performed to decipher the relation between the persistent fmd virus (fmdv) infection and cellular immune response in indian cattle (bosindicus) following experimental inoculation of fmdv asia 1. persistent viral infection (carriers) was detected by antigen capture rt-pcr on the oesophageal-pharyngeal ...201020189208
a novel system for the production of high levels of functional human therapeutic proteins in stable cells with a semliki forest virus noncytopathic vector.semliki forest virus (sfv) vectors lead to high protein expression in mammalian cells, but expression is transient due to vector cytopathic effects, inhibition of host cell proteins and rna-based expression. we have used a noncytopathic sfv mutant (ncsfv) rna vector to generate stable cell lines expressing two human therapeutic proteins: insulin-like growth factor i (igf-i) and cardiotrophin-1 (ct-1). therapeutic genes were fused at the carboxy-terminal end of puromycin n-acetyl-transferase gene ...201020188220
limiting the impacts of foot and mouth disease in large ruminants in northern lao people's democratic republic by vaccination: a case study.foot and mouth disease (fmd) is the most important global transboundary livestock disease and is endemic in lao people's democratic republic (lao pdr) with outbreaks occurring regularly. lao pdr shares borders with five countries and as a major thoroughfare for transboundary livestock movement, is vulnerable to the social and economic impacts of fmd. the fmd outbreak occurred in january 2009 in the pek district, located in the north-eastern lao pdr province of xieng khuang and involved all 111 v ...201020180923
transgenic mouse model integrating sirna targeting the foot and mouth disease virus.we have constructed 2 small interfering rnas (sirnas) specifically targeting homogenous 3d and 2b1 regions of 7 serotypes of the foot and mouth disease virus (fmdv) and tested the ability of sirnas to inhibit virus replication in baby hamster kidney (bhk-21) cells and suckling mice. in this study, we generated transgenic mouse models integrating short hairpin rna (shrna) targeting microinfected fmdv. when examined at the 7th passage in transgenic mice, the target gene was still found by pcr to b ...201020176056
quantitative single serum-dilution liquid phase competitive blocking elisa for the assessment of herd immunity and expected protection against foot-and-mouth disease virus in vaccinated cattle.a single serum-dilution liquid phase elisa (slpelisa) was standardized to be used for serological evaluation of herd immunity against foot-and-mouth disease. the absorbance value at a dilution 1:64 of each serum sample was interpolated in a standard curve by plotting the antibody titers of six control sera determined by end point dilution liquid phase elisa (lpelisa), against the absorbance values for the same control sera at 1:64 dilutions. a straight line was obtained by linear regression anal ...201020170683
hsp70 enhances presentation of fmdv antigen to bovine cd4+ t cells in vitro.foot-and-mouth disease virus (fmdv) is the causative agent of a highly contagious acute vesicular disease affecting cloven-hoofed animals, including cattle, sheep and pigs. the current vaccine induces a rapid humoral response, but the duration of the protective antibody response is variable, possibly associated with a variable specific cd4+ t cell response. we investigated the use of heat shock protein 70 (hsp70) as a molecular chaperone to target viral antigen to the major histocompatibility co ...201020167197
attenuated salmonella choleraesuis-mediated rnai targeted to conserved regions against foot-and-mouth disease virus in guinea pigs and swine.in this study, specific sequences within three genes (3d, vp4 and 2b) of the foot-and-mouth disease virus (fmdv) genome were determined to be effective rnai targets. these sequences are highly conserved among different serotype viruses based on sequence analysis. small interfering rna (sirna)-expressing plasmids (p3d-nt19, p3d-nt56, pvp4-nt19, pvp4-nt65 and p2b-nt25) were constructed to express sirna targeting 3d, vp4 and 2b, respectively. the antiviral potential of these sirna for various fmdv ...201020167192
recombinant dna and protein vaccines for foot-and-mouth disease induce humoral and cellular immune responses in mice.foot-and-mouth disease virus (fmdv) is a small single-stranded rna virus which belongs to the family picornaviridae, genus apthovirus. it is a principal cause of fmd which is highly contagious in livestock. in a wild type virus infection, infected animals usually elicit antibodies against structural and non-structural protein of fmdv. a structural protein, vp1, is involved in neutralization of virus particle, and has both b and t cell epitopes. a rna-dependent rna polymerase, 3d, is highly conse ...200920157614
a bicistronic lentiviral vector based on the 1d/2a sequence of foot-and-mouth disease virus expresses proteins stoichiometrically.classic ires sequences are notorious for exerting biased expression in favor of upstream coding regions when placed into polycistronic vectors. here, we report the development of a bicistronic lentiviral system based on the 1d/2a sequence from the foot-and-mouth disease virus that is able to maintain tightly balanced control of upstream and downstream protein expression for several days at a stoichiometry very closely approaching 1.0. our results suggest that the 1d/2a sequence can be optimized ...201020132845
loss of plasmacytoid dendritic cell function coincides with lymphopenia and viremia during foot-and-mouth disease virus infection.foot-and-mouth disease virus (fmdv) causes an acute, highly contagious disease of livestock. though fmdv is very sensitive to interferon-alpha (ifn-alpha), ifn-beta, and ifn-gamma, the virus has evolved mechanisms to evade such innate responses. for instance, during acute infection, fmdv suppresses ifn-alpha production by skin and myeloid dendritic cells (dcs). we have previously reported that fmdv infection induces a transient lymphopenia and interruption of t-lymphocyte responses to mitogenic ...201020121400
iga antibody response of swine to foot-and-mouth disease virus infection and vaccination.foot-and-mouth disease virus (fmdv) continues to be a significant economic problem worldwide. control of the disease involves the use of killed-virus vaccines, a control measure developed decades ago. after natural infection, the primary site of replication of fmdv is the pharyngeal area, suggesting that a mucosal immune response is the most effective. humoral immunity to killed-virus vaccination induces antibodies that can prevent the clinical disease but not local infection. determining whethe ...201020107003
development of an immunochromatographic strip for the detection of antibodies against foot-and-mouth disease virus serotype o.an immunochromatographic strip was developed for the serological detection of type o foot-and-mouth disease (fmd) in swine. in the strip, the expressed protein of vp1, the main protective antigen of fmdv, labeled with colloidal gold was used as the detector, the staphylococcal protein a (spa) and swine anti-foot-and-mouth disease virus (fmdv) antibody were blotted on the nitrocellulose membrane for the test and control lines, respectively. 296 swine serum samples were collected to evaluate the c ...201020100515
molecular characterization of serotype a foot-and-mouth disease viruses circulating in vietnam in 2009.foot-and-mouth disease (fmd) is a major cause of endemic outbreaks in vietnam in recent years. in this work, six serotype a foot-and-mouth disease viruses (fmdv), collected from endemic outbreaks during january and february of 2009 in four different provinces in vietnam, were genetically characterized for their complete genome sequences. genetic analysis based on the complete viral genome sequence indicated that they were closely related to each other and shared 99.0-99.8% amino acid (aa) identi ...201020097490
possible use of rna isolate from inactivated vaccine for external positive control in reverse transcription-based detection of foot-and-mouth disease virus in bull semen.this study has demonstrated the novel use of inactivated and purified vaccine against fmd virus for detection and analysis. rna isolate was efficiently generated from the vaccine for an external positive control for reverse transcription polymerase chain reaction (rt-pcr) and reverse transcription loop-mediated isothermal amplification (rt-lamp) assays. the target dna fragment sequences from the 2b region and 3d rna polymerase gene of the virus for rt-pcr and rt-lamp respectively were successful ...201020097168
competition-colonization dynamics in an rna virus.during replication, rna viruses rapidly generate diverse mutant progeny which differ in their ability to kill host cells. we report that the progeny of a single rna viral genome diversified during hundreds of passages in cell culture and self-organized into two genetically distinct subpopulations that exhibited the competition-colonization dynamics previously recognized in many classical ecological systems. viral colonizers alone were more efficient in killing cells than competitors in culture. ...201020080701
phylogenetic analysis of indian serotype asia1 foot-and-mouth-disease virus isolates revealed emergence and reemergence of different genetic lineages.foot-and-mouth-disease virus (fmdv) serotype asia1 causes significant number of disease outbreaks in india. indian asia1 virus isolates were shown to be genetically heterogeneous and of the two lineages (lineage b and lineage c) described in india, lineage c caused majority of the outbreaks. emergence of a novel divergent lineage (lineage d) within lineage c has been described in 2001. in the present report, the complete vp1 genomic region of 41 fmdv asia1 field isolates collected between 2003 a ...201020080365
effect of the extract made from cochinchina momordica seeds on the humoral immune responses of mice to a commercial foot-and-mouth disease vaccine (serotypes o and asia 1).the extract from ecms was investigated for its effect on the humoral immune responses to foot-and-mouth disease vaccination. fifty-six mice were randomly divided into seven groups with eight animals in each. mice in groups 5 to 7 were subcutaneously (s.c.) injected with 0.5 mg dex daily for 4 days to induce immunosuppression. the animals were then orally given ecms (200 microg in 250 microl saline) in groups 3 and 6 or 250 microl saline in group 2, or s.c. injected with ecms (50 microg in 100 mi ...201020055940
a single amino acid substitution in the capsid of foot-and-mouth disease virus can increase acid lability and confer resistance to acid-dependent uncoating inhibition.the acid-dependent disassembly of foot-and-mouth disease virus (fmdv) is required for viral rna release from endosomes to initiate replication. although the fmdv capsid disassembles at acid ph, mutants escaping inhibition by nh(4)cl of endosomal acidification were found to constitute about 10% of the viruses recovered from bhk-21 cells infected with fmdv c-s8c1. for three of these mutants, the degree of nh(4)cl resistance correlated with the sensitivity of the virion to acid-induced inactivation ...201020053737
the effect of foot-and-mouth disease (fmd) vaccination on virus transmission and the significance for the field.vaccination against foot-and-mouth disease (fmd) might be one of the control measures used during an fmd epidemic depending on the local epidemiological situation, the status of the country, and the opinion of policy makers. a sound decision on vaccination can be made only if there is sufficient scientific knowledge on the effectiveness of vaccination in eliminating the virus from the population. an important question is whether a single vaccination applied as an emergency vaccine can contribute ...200920046605
foot-and-mouth disease viral loads in pigs in the early, acute stage of disease.the progress and pathogenesis of foot-and-mouth disease virus (fmdv) was studied in infected pigs by observing the development of clinical signs in two separate experiments. viral loads were determined by real-time quantitative rt-pcr in the liver, spleen, cervical lymph node, mandibular lymph node, retropharyngeal lymph node, soft palate, pharynx, tonsil, tongue and skin (coronary band area). tissue samples were collected from both inoculated and contact-infected pigs at several time points dur ...201020045852
high expression level of a foot and mouth disease virus epitope in tobacco transplastomic plants.chloroplast transformation has an extraordinary potential for antigen production in plants because of the capacity to accumulate high levels of recombinant proteins and increased biosafety due to maternal plastid inheritance in most crops. in this article, we evaluate tobacco chloroplasts transformation for the production of a highly immunogenic epitope containing amino acid residues 135-160 of the structural protein vp1 of the foot and mouth disease virus (fmdv). to increase the accumulation le ...201020041332
rt-pcr evaluation for identification and sequence analysis of foot-and-mouth disease serotype o from 2006 to 2007 in punjab, pakistan.fmd clinically positive 250 tissue samples (mouth and hoof epithelium and vesicle swabs, tongue tissue) and 175 secretion samples (milk, saliva, serum, plasma) were evaluated by rt-pcr for the diagnosis of fmd with different pair of universal and serotype-specific primers from 2006 to 2007 in punjab, pakistan. universal primer pair p1/p2 from vp1 gene detected fmd in 182 out of 250 (72.8%) tissues and 92 out of 175 (52.6%) secretion samples, while universal primer 1f/1r from 5'utr region detecte ...201120031216
design and optimization of a novel reverse transcription linear-after-the-exponential pcr for the detection of foot-and-mouth disease virus.a novel molecular assay for the detection of foot-and-mouth disease virus (fmdv) was developed using linear-after-the-exponential polymerase chain reaction (late-pcr).201020028437
molecular cloning and phylogenetic analysis of integrins alphavbeta1 and alphavbeta6 of one-humped camel (camelus dromedarius).bactrian camels can relatively easily be infected with fmdv, but dromedary camels remain resistant even to high doses of the virus. to understand the different susceptibility between the two camel species from the standpoint of viral receptors, this work reports the sequences of the dromedary camel integrin cdnas encoding alphavbeta1 and alphavbeta6 and compare them to those of other species, especially to bactrian camels. the complete coding sequences for the dromedary camel alphav, beta1 and b ...201020015555
recovery of infectious foot-and-mouth disease virus from full-length genomic cdna clones using an rna polymerase i system.the prototypic foot-and-mouth disease virus (fmdv) was shown more than a century ago to be the first filterable agent capable of causing fmd, and it has served as an important model for studying basic principles of aphthovirus molecular biology. however, the complex structure and antigenic diversity of fmdv have posed a major obstacle to the attempts at manipulating the infectious virus by reverse genetic techniques. here, we report the recovery of infectious fmdv from cdnas based on an efficien ...200920011974
rna immunization can protect mice against foot-and-mouth disease virus.in previous work we have reported the immunization of swine using in vitro-transcribed foot-and-mouth disease virus (fmdv) rna. with the aim of testing whether rna-induced immunization can mediate protection against viral infection, a group of swiss adult mice was inoculated with fmdv infectious transcripts. in most inoculated animals viral rna was detected in serum at 48-72h postinoculation. a group of the rna-inoculated mice (11 out of 19) developed significant titers of neutralizing antibodie ...201020005905
molecular characterization of sat 2 foot-and-mouth disease virus from post-outbreak slaughtered animals: implications for disease control in uganda.in uganda, limiting the extent of foot-and-mouth disease (fmd) spread during outbreaks involves short-term measures such as ring vaccination and restrictions of the movement of livestock and their products to and from the affected areas. in this study, the presence of fmd virus rna was investigated in cattle samples 3 months after fmd quarantine measures had been lifted following an outbreak in 2004. oropharyngeal tissue samples were obtained from 12 cattle slaughtered in a small town abattoir i ...201020003615
currently important animal disease management issues in sub-saharan africa.the present international approach to management of transboundary animal diseases (tads) is based on the assumption that most can be eradicated; consequently, that is the usual objective adopted by international organizations concerned with animal health. however, for sub-saharan africa and southern africa more particularly, eradication of most tads is impossible for the foreseeable future for a variety of technical, financial and logistical reasons. compounding this, the present basis for acces ...200919967938
interferon-induced protection against foot-and-mouth disease virus infection correlates with enhanced tissue-specific innate immune cell infiltration and interferon-stimulated gene expression.previously, we demonstrated that type i interferon (ifn-alpha/beta) or a combination of ifn-alpha/beta and type ii ifn (ifn-gamma) delivered by a replication-defective human adenovirus 5 (ad5) vector protected swine when challenged 1 day later with foot-and-mouth disease virus (fmdv). to gain a more comprehensive understanding of the mechanism of protection induced by ifns, we inoculated groups of six swine with ad5-vectors containing these genes, challenged 1 day later and euthanized 2 animals ...201019955313
cd40-expressing plasmid induces anti-cd40 antibody and enhances immune responses to dna vaccination.various approaches have been used to improve the efficacy of dna vaccination, including the incorporation of molecular adjuvants. because the cd40 ligand-cd40 interaction plays a major role in initiating immune responses, we sought to develop a molecular adjuvant targeting this interaction.201019950201
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