WO2019147891A1 - Compositions et méthodes de détermination de sensibilité au virus de la grippe aviaire - Google Patents

Compositions et méthodes de détermination de sensibilité au virus de la grippe aviaire Download PDF

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WO2019147891A1
WO2019147891A1 PCT/US2019/015081 US2019015081W WO2019147891A1 WO 2019147891 A1 WO2019147891 A1 WO 2019147891A1 US 2019015081 W US2019015081 W US 2019015081W WO 2019147891 A1 WO2019147891 A1 WO 2019147891A1
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protein
binding
individual
influenza
virus
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WO2019147891A9 (fr
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Xi Jason JIANG
Ming Tan
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Children's Hospital Medical Center
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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/569—Immunoassay; Biospecific binding assay; Materials therefor for microorganisms, e.g. protozoa, bacteria, viruses
    • G01N33/56983—Viruses
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
    • G01N2333/005—Assays involving biological materials from specific organisms or of a specific nature from viruses
    • G01N2333/08—RNA viruses
    • G01N2333/11—Orthomyxoviridae, e.g. influenza virus

Definitions

  • Influenza A viruses are enveloped RNA viruses in the family Orthomyxoviridae. They exhibit a broad host range infecting both humans and various animal species, including wild birds, poultry, pigs, dogs, cats, horses, mink, bats, and marine mammals, among which waterfowl are believed to be IAV reservoirs.
  • human flus can be sorted into several types, including seasonal flu that spreads rapidly and widely within human populations without involvement of specific animal vectors, avian flu that is transmitted from birds/chicken, and swine flu that is communicated from domestic pigs.
  • the method may comprise the steps of a) contacting a saliva sample obtained from said individual with a probe comprising a head portion of the of hemagglutinin 1 (HA1) of the H7N9 Influenza A vims (the“H7 HA1 protein”); b) detecting the probe bound to a binding component in the saliva sample of an individual whose status is desired to be known, and characterizing the individual as having either a binder status or a nonbinder status based on the amount of probe bound to said binding component.
  • a binder status indicates that the individual is susceptible to H7N9 infection; and a non-binder status indicates that the individual is not susceptible to H7N9 infection.
  • FIG 1A-1D Production and validation of functional H7 HA1 protein.
  • FIG 1A- 1D The H7 HA1 proteins in forms of GST-HA1 fusion proteins (1A, 1B) and S60-HA1 particles (1C, 1D) were produced in E. coli. Their expression constructs are schematically illustrated in a (GST-fusion protein) and 1C (norovirus S domain fusion protein), while the expressed and purified proteins were analyzed by SDS-PAGE, respectively (1B, 1D). Lane M is the pre-stained protein markers with indicated sizes. The remaining three lanes are three purified protein fractions that eluted from the affinity column.
  • FIG 2A-2D Associations between the S60-HA1 protein-binding signals of the saliva samples and H7N9 vims infection.
  • 2A Results of EIA-based binding assays measuring the binding signals between the S60-HA1 protein and the 92 tested saliva samples, which were sorted by their signal intensities.
  • FIG 3A-3F Assessments of associations between the salivary SLe x /SLe a phenotypes and H7N9 virus infection. Comparisons of the SLe x phenotypes between the patients and the two uninfected controls in three combinations: 3 A. patients vs. control G;
  • FIG 4A-4F Assessments of associations between the SNL- and MAL I- binding signals to saliva samples and H7N9 infection.
  • 4A-4C Comparisons of the SNL- binding signals to the saliva samples between the patients and the two uninfected controls in three combinations: 4A: patients vs. control G; 4B: patients vs. control M; 4C: patients vs. controls G + M.
  • 4D-4F Comparisons of the MAL I-binding signals to the saliva samples between the patients and the two uninfected controls in three combinations: 4D: patients vs. control G; 4E: patients vs. control M; 4F: patients vs. controls G + M.
  • Y-axis indicates signal intensities, while X-axis showed the compared experimental groups.
  • the statistical differences between data groups are analyzed by t-test (t) as well as Welch’s t-test (wt) and their P values (Pt and Pwt) are shown and indicated by asterisks (*P ⁇ 0.05; ns, P > 0.05).
  • FIG 5A-5I Assessments of associations between HBGAs, including A, B, Hl phenotypes and H7N9 virus infection.
  • FIG 6A-6L Assessments of associations between Le a , Le b , Le x , and Le y phenotypes and H7N9 virus infection.
  • the term“about” or“approximately” means within an acceptable error range for the particular value as determined by one of ordinary skill in the art, which will depend in part on how the value is measured or determined, e.g., the limitations of the measurement system.
  • “about” may mean within 1 or more than 1 standard deviation, per the practice in the art.
  • “about” may mean a range of up to 20%, or up to 10%, or up to 5%, or up to 1% of a given value.
  • the term may mean within an order of magnitude, preferably within 5- fold, and more preferably within 2-fold, of a value.
  • the term refers to a human patient, but the methods and compositions may be equally applicable to non-human subjects such as other mammals. In some embodiments, the terms refer to humans. In further embodiments, the terms may refer to children.
  • sequence identity indicates a nucleic acid sequence that has the same nucleic acid sequence as a reference sequence, or has a specified percentage of nucleotides that are the same at the corresponding location within a reference sequence when the two sequences are optimally aligned.
  • a nucleic acid sequence may have at least 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identity to the reference nucleic acid sequence.
  • the length of comparison sequences will generally be at least 5 contiguous nucleotides, preferably at least 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, or 25 contiguous nucleotides, and most preferably the full length nucleotide sequence.
  • Sequence identity may be measured using sequence analysis software on the default setting (e.g., Sequence Analysis Software Package of the Genetics Computer Group, University of Wisconsin Biotechnology Center, 1710 University Avenue, Madison, Wis. 53705). Such software may match similar sequences by assigning degrees of homology to various substitutions, deletions, and other modifications.
  • Influenza A viruses are enveloped RNA viruses in the family
  • Orthomyxoviridae They exhibit a broad host range infecting both humans and various animal species, including wild birds, poultry, pigs, dogs, cats, horses, mink, bats, and marine mammals, among which water fowl are believed to be IAV reservoirs.
  • human flus can be sorted into several types, including seasonal flu that spreads rapidly and widely within human populations without involvement of specific animal vectors, avian flu that is transmitted from birds/chicken, and swine flu that is communicated from domestic pigs.
  • Avian influenza viruses mainly circulate in wild birds and some of them infect chicken causing large outbreaks in chicken farms, leading significant economic loss.
  • HPAI highly pathogenic avian influenza
  • HPAI H5N1 and HPAI H7N9 viruses cause human infections with high mortality rates
  • HPAI H7N3 viruses cause only mild disease in humans.
  • the recently emerged H7N9 avian flu viruses in 2013 in China have caused five epidemic waves, infecting totally 1344 people with 511 deaths in China 1 , becoming a new public health threat.
  • the method may comprise the steps of a) contacting a saliva sample obtained from said individual with a probe comprising a head portion of the of hemagglutinin 1 (HA1) of the H7N9 Influenza A vims (the“H7 HA1 protein”); b) detecting the probe bound to a binding component in the saliva sample of an individual whose status is desired to be known, and characterizing the individual as having either a binder status or a nonbinder status based on the amount of probe bound to said binding component.
  • a binder status indicates that the individual is susceptible to H7N9 infection; and a non-binder status indicates that the individual is not susceptible to H7N9 infection.
  • the head portion of HA1 is also known as the receptor-binding domain (RBD) (223 amino acids) of the hemagglutinin (HA) of the H7N9 influenza A vims.
  • RBD receptor-binding domain
  • the term“head portion of the HA1 of the H7N9 Influenza A vims includes sequences having about 90% homology, or about 91% homology, or about 92% homology, or about 93% homology, or about 94% homology, or about 95% homology, or about 96% homology, or about 97% homology, or about 98% homology, or about 99% homology, or 100% homology to SEQ ID NO 1.
  • variance of the sequence can occur provided that the protein sequence that contains all or a portion of the receptor binding domain retains structure sufficient to carry out the disclosed methods (i.e., binding to the binding component).
  • the H7 HA1 protein may be recombinantly produced using methods readily known in the art.
  • the probe may comprise a detectable tag, such tags being readily understood by one of ordinary skill in the art.
  • the detectable tag may comprise glutathione S-transferase (GST).
  • the detectable tag may comprise an Seo protein as disclosed in Xia et al, Bioengineered Norovirus S60 Nanoparticles as a Multifunctional Vaccine Platform. ACS Nano. 2018. PubMed PMID: Medline:30234973.
  • the detecting step may comprise detecting a detectable tag operatively connected to the probe.
  • the detecting step may comprise contacting an Influenza A Vims (IAV) H7-specific antibody to the mixture of probe and saliva.
  • the binding component may be a glycan present in the saliva sample that binds selectively to the H7 HA1 protein.
  • the binding status may be determined by first measuring an optical density using methods described herein, more particularly, using an EIA-binding assay, for example, wherein the probe comprises an S60 tag.
  • an individual is considered to have a“binder status” when the solution containing the saliva sample and the probe has an OD of greater than about 0.13, or greater than about 0.14, or greater than about 0.15, or greater than about 0.16, or greater than about 0.17, or greater than about 0.18, or greater than about 0.19, or greater than about 0.20, or greater than about 0.21, or greater than about 0.22, or greater than about 0.23, or greater than about 0.24, or greater than about 0.25, or greater than about 0.26, or greater than about 0.27.
  • the binder may be considered a“high binder,” wherein a high binder provides a sample having an OD of greater than about 0.27.
  • the binding status may be determined by first measuring an optical density using methods described herein, more particularly, using an EIA-binding assay, for example, wherein the probe comprises an S60 tag.
  • an individual is considered to have a“binder status” when the solution containing the saliva sample and the probe has an OD of less than about 0.13, or less than about 0.14, or less than about 0.15, or less than about 0.16, or less than about 0.17, or less than about 0.18, or less than about 0.19, or less than about 0.20, or less than about 0.21, or less than about 0.22, or less than about 0.23, or less than about 0.24, or less than about 0.25, or less than about 0.26, or less than about 0.27.
  • a composition comprising a probe comprising the head portion of the of hemagglutinin 1 (HA1) of the H7N9 Influenza A vims (“H7 HA1 protein”) and a saliva sample obtained from an individual is disclosed.
  • the composition may comprise H7 HA1 protein is conjugated to a detectable tag, and a saliva sample obtained from an individual.
  • the composition may include one or more carriers for use with a saliva sample.
  • a preservative may be employed to increase the shelf life of the protein.
  • a preservative useful for a protein may include, for example, an antimicrobial preservative, such as M-cresol, phenol, benzyl alcohol, or other alcohols known in the art.
  • a suitable concentration of the preservative may be from about 0.02% to about 2% based on the total weight of the composition, although larger or smaller amounts may be desirable depending upon the agent selected.
  • the formulations may be isotonic with the predicted saliva sample. The isotonicity of the compositions may be attained using sodium tartrate, propylene glycol or other inorganic or organic solutes. An example includes sodium chloride.
  • Buffering agents may be employed, such as acetic acid and salts, citric acid and salts, boric acid and salts, and phosphoric acid and salts.
  • Parenteral vehicles include sodium chloride solution, Ringer’s dextrose, dextrose and sodium chloride, lactated Ringer’s or fixed oils.
  • Intravenous vehicles include fluid and nutrient replenishers, electrolyte replenishers (such as those based on Ringer’s dextrose), and the like.
  • the compositions may comprise stabilizing components such as human serum albumin or bovine serum albumin.
  • IAVs Influenza A viruses
  • SA sialic acid
  • Gal SA-galactose
  • H7N9 IAV infections Applicant characterized variations of human susceptibility to H7N9 IAV infections by testing saliva samples.
  • Saliva samples have been widely used to study pathogen-host interaction to assess host susceptibility to infections of noroviruses and rotaviruses, which is associated with the host histo-blood group antigens (HBGAs) and SA- related carbohydrates 8-12 .
  • H7 hemagglutinin (HA) As a probe, Applicant found a strong association between H7 HA-saliva-binding signals and H7N9 virus infection among saliva samples from patients and uninfected controls.
  • H7 HA1 protein in forms of GST-HA1 fusion proteins (FIG 1A, B) and S60-HA1 particles (FIG. 1C, 1D) were produced as soluble proteins at yields of 7-10 mg/liter bacterial culture. While a previous study showed that Escherichia coli-expressed IAV HA1 protein folds into its native structure with an intact receptor-binding site 13 , Applicant further demonstrated here that both GST- and S60-HA1 fusion proteins reacted with IAV H7- specific antibody (LifeSpan BioSciences, Inc.) strongly by enzyme immunoassays (EIA)
  • FIG. 1E agglutinated human and chicken red blood cells (RBCs) with higher hemagglutination activity of the S60-HA1 than that of GST-HA1
  • FIG. 1F The heat- inactivated HA1 fusion proteins reduced their reactivity to the H7 antibody significantly, suggesting the loss of the conformational epitopes via the heat treatment (FIG. 1E).
  • Applicant then showed that the two HA1 proteins bound a2,3-, but not a2,6- or a2,8-linked sialyl glycans (FIG. 1G, 1H), consistent with the results reported by others 7 14 15 .
  • the S60-HA1 protein gave higher and cleaner binding signals than those of the GST-HA1 fusion protein (FIG. 1, compared 1G with 1H), likely due to the high avidity of the S60-HA1 particles compared with the bivalent GST-HA1 protein.
  • the S60-HA1 proteins were used for the downstream saliva-binding experiments.
  • H7 HAl-saliva-binding signals were associated with H7N9 virus infection in humans
  • EIA-based binding assays showed that the S60-HA1 protein bound 27 (29%) of 92 tested saliva samples with optical density (OD) > 0.13, but not the remaining 65 (71%) ones, segregating the saliva samples into binder and non-binder subpopulations (FIG. 2A, Table 1). Significantly higher binding signals (FIG. 2D) and higher binding percentage (Table 1) of the S60-HA1 protein to the saliva samples of the patients than those to the uninfected controls were found, indicating an association between the H7 HAl-saliva- binding signals and human susceptibility to H7N9 avian influenza viruses.
  • Salivary SLe x signals were associated with H7N9 virus infection in humans
  • Applicant performed HBGA phenotyping of the saliva samples for glycan factors possibly associated with H7N9 vims infection.
  • glycan factors possibly associated with H7N9 vims infection.
  • the signals of SLe x antigens were found to be associated with H7N9 infection in humans (FIG. 3A, 3C, 3E).
  • no such association was found for the other eight HBGAs, including A, B, Hl, Le a , Le b , Le x , and Le y , as well as SLe x (FIGS 3B, 3D, 3F, 4A-4F, and 5A-5L).
  • SLe x antigens may be a host susceptibility factor of avian H7N9 virus to humans.
  • the SLe x antigen signals of the saliva samples were compared with the binding signal profile of H7 HA1, no association between the two sets of data were seen; specifically, 46 (50%) saliva samples are SLe x -positive (FIG. 3E, Table 1), while only 27 (29%) saliva samples bound H7N9 HA1 (FIG. 2D, Table 1).
  • Table 1 Salivary SLe x phenotypes and saliva-binding results to the H7 HA1 protein of H7N9-infected patients and uninfected control groups a. These were confirmed flu patients infected by H7N9 influenza viruses b. These were uninfected control individuals who had similar avian exposure as that of the patients c. These were uninfected control individuals who had close contact with the patients
  • Saliva samples have become a widely used reagent to study pathogen-host interactions for assessment of anti-pathogen activity and host susceptibility of pathogens that recognize salivary carbohydrates as ligands or receptors, including norovirus 8-10 16 , rotavirus 11 12 , Candida albicans 17 , and influenza viruses 18 .
  • Applicant’s current study demonstrated significantly higher H7 HA-binding signals to the saliva samples from the H7N9-infected patients than those from the uninfected controls who either had similar avian exposure as patients (control G) or had close contact with the patients (control M). These data indicated that the saliva-based binding assays may be used to study and even predict human susceptibility to H7N9 infection.
  • HBGA phenotyping and lectin-binding profiles of the saliva samples also showed associations between H7N9 infection and salivary SLe x phenotypes and SNL-binding signals, consisting with the previous findings that several types of avian influenza viruses recognize certain SAs and SLe x antigens 5,6 .
  • SAs and SLe x antigens 5,6 recognize certain SAs and SLe x antigens 5,6 .
  • H7N9- infected patients All 32 H7N9- infected patients were confirmed by PCR using H7- and N9-encoding gene-specific primers, some of the cases were further confirmed by H7N9 vims isolation and sequencing, but still 13 cases were not yet further confirmed by vims isolation and sequencing.
  • SLe x is a ligand of the two probes
  • additional residues adjacent to SLe x moiety may participate in the binding and thus determine the binding specificity of H7 HA.
  • This scenario might be similar to the complex binding interfaces of human rotaviruses that recognize stmcturally related HBGAs with different terminal and internal residues being responsible for strain-specific host ranges as a result of selection by the polymorphic HBGAs in rotavims evolution 19,20 .
  • IAVs also have a segmented RNA genome, recognizing carbohydrate receptors, including SAs, and interacting with glycan receptors via the surface protmding proteins (HA).
  • H7N9 vims might also result from host selection, similar to that of rotaviruses. While majority of avian flu vimses recognizing certain SAs and/or SLe x antigens and maintained well in avian populations, H7N9 viruses could bind additional residues adjacent to SLe x , gaining further ability to infect humans.
  • Applicant’ s study suggests a new thinking about the strategy of disease control and prevention against H7N9 flu epidemics. For example, workers who need to expose to avian, such as those working in chicken farms and chicken product industries may be screened using saliva samples and an H7 HA probe for their susceptibility to the viruses and avoid such positions, if they are high binders (OD greater than about 0.275). The screen strategy may also be applied to the general populations for self-protection purposes to avoid avian exposure. In addition, Applicant’s study may also help risk assessment on whether a large-scale killing of chicken/ducks as risk control methods may be necessary. Finally, Applicant’s study suggested that the chance of avian influenza virus-caused large outbreaks or pandemics might be lower than previously thought.
  • EPI1103237, and EPI1103239 (A/Jiangsu/ 08190/2017); EPI1103252-EPI1103257,
  • EPI1103259, and EPI1103260 (A/Jiangsu/08l92/20l7); EPI1103294- EPI1103298,
  • EPI1103300, EPI1103301, and EPI1103304 (A/ Jiangsu/08l97/20l7); EPI971205- EPI971212 (A/Jiangsu/ 11586/2017); EPI971197-EPI971204 (A/Jiangsu/ll 588/ 2017); EPI971173-EPI971180 (A/Jiangsu/l 1589/2017); EPI 1103185, EPI1103187-EPI1103190, EPI1103192, EPI1103 193, and EPI1103195 (A/Jiangsu/08l86/20l6); EPI1103365,
  • EPI1103366 EPI1103368-EPI1103370, and EPI1103372- EPI1103374
  • the saliva samples were prepared according to Applicant’s previous study 22 . Briefly, the saliva samples were boiled for 10 min to inactivate protein components, including antibodies. The boiled samples were then centrifuged to remove unwanted cells/debris by centrifugation at 10 000 rpm for 5 min on a bench-top centrifuge. The samples were store at -70 °C. The saliva samples were diluted lOOO-folds before they were coated to micro titer plates.
  • the receptor-binding HA1 head (223 residues, spanning from C32 to N254) of the H7 protein of an H7N9 vims isolate A/Jiangsu/60462/2016 that infected the patients of this study was produced via the E. coli system in two forms, a GST-H7 HA1 fusion protein and a norovirus S60 particle (as described in Xia M, Huang P, Sun C, Han L, Vago FS, Li K, et al. Bioengineered Norovirus Seo Nanoparticles as a Multifunctional Vaccine Platform.
  • HA1 protein (referred as S60-H7 HA1).
  • S60-H7 HA1 fusion protein the H7 HA1 protein was fused directly to the GST tag using the plasmid pGEX-4T-l of the GST-Gene Fusion System (GE).
  • H7 HA1 protein was fused to the modified norovirus S domain via a short linker (M.T. and X.J., unpublished data).
  • a Hisx6 tag was fused to the end of the H7 HA1 for purification purpose. Both proteins were expressed in E. coli as described elsewhere 23 ’ 24 .
  • the bound S60-HA1 proteins were detected by in-house-made guinea pig hyperimmune serum against norovirus-like particles (VLPs) 26 that recognize the S60 particles.
  • VLPs norovirus-like particles
  • the bound Guinea pig antibody was then detected by rabbit anti-guinea pig IgG-HRP conjugate as described elsewhere 23 27 .
  • Five percent nonfat milk in lx PBS was used as diluent for H7 HA1 protein and the antibodies. Plates were washed five times between above steps using washing solution with 0.05% Tween 20. Wells with 5% nonfat milk without a saliva sample were used as negative controls.
  • the ABH and Lewis HBGAs in the saliva samples were determined by EIAs using corresponding Mabs against individual HBGAs (A, B, Hl, Lea, Le b , Le x , Le y , SLe a , and SLe x , purchased from Invitrogen and Biolengend) as described previously22,26. Briefly, saliva-coated microtiter plates (Immulon high binding polystyrene microtiter plates, Thermo Scientific) were blocked with 5% nonfat milk, followed by incubation with Mabs against individual HBGAs. The bound Mabs were then detected by a secondary antibody-HRP conjugates.
  • saliva-coated microtiter plates Immulon high binding polystyrene microtiter plates, Thermo Scientific
  • Saliva samples were coated on microtiter plates (Immulon high binding polystyrene microtiter plates, Thermo Scientific). After blocking with 5% nonfat milk biotinylated SNL and MAL I at 10 pg/ml were added to saliva-coated wells separately and incubated for 60 min. The bound SNL or MAL I was detected by streptavidin-HRP conjugates (Jackson ImmunoResearch, West Grove, PA). The signal intensity was measured at OD450. Lectins measurement allows the background sialic related carbohydrate content in human saliva to be determined.
  • the bound GST-HA1 or S60-HA1 protein proteins were detected by Applicant’ s in-house-made rabbit hyper- immune serum against GST or guinea pig hyperimmune serum against norovirus VLPs that recognize the S60 particles, followed by the detection of rabbit/guinea pig antibodies using specific secondary antibody- HRP conjugates, as described above.
  • H7 HA1 proteins were shown by sodium dodecyl sulfate polyacrylamide gel electrophoresis gel, while binding signals of the H7 HA1 protein to sialyl glycans were shown by column graphics with indications of means (columns) and corresponding standard deviations (error bars) (FIG. 1). Binding and non-binding populations of all tested saliva samples were shown by binding a curve in the order of binding signals from low to high with an indication of the starting of the binding signal by an arrow (FIG. 2A). All remaining data were shown by grouped point graphics, in which each data point represents a single saliva sample that were a mean of triplicated or duplicated experiments. The means (the middle wider lines) and the error bars (the upper and lower narrow lines) for all data points were shown. Statistical differences among data sets were calculated by softwares GraphPad Prism 6 (GraphPad Software, Inc). Applicant first performed unpaired t-
  • Gambaryan, A. S. et al. 6-sulfo sialyl Lewis X is the common receptor determinant recognized by H5, H6, H7 and H9 influenza viruses of terrestrial poultry. Virol.
  • Tan, M. & Jiang, X. Norovirus and its histo-blood group antigen receptors an answer to a historical puzzle. Trends Microbiol. 13, 285-293 (2005).

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Abstract

L'invention concerne des méthodes d'identification d'un individu comme étant sensible à un virus de la grippe aviaire H7N9 ou non sensible à un virus de la grippe aviaire H7N9. Selon un aspect, la méthode peut consister a) à mettre en contact un échantillon de salive obtenu chez ledit individu avec une sonde comprenant une partie de tête de l'hémagglutinine 1 (HA1) du virus de la grippe A H7N9 (la "protéine H7 HA1") ; b) à détecter la liaison de la sonde à un composant de liaison dans l'échantillon de salive d'un individu dont on souhaite connaître l'état, et à caractériser l'individu comme présentant soit un état de liaison soit un état de non-liaison en fonction de la quantité de liaison de sonde audit composant de liaison. Selon un aspect, un état de liaison indique que l'individu est sensible à une infection par H7N9 ; et un état de non-liaison indique que l'individu n'est pas sensible à une infection par H7N9.
PCT/US2019/015081 2018-01-26 2019-01-25 Compositions et méthodes de détermination de sensibilité au virus de la grippe aviaire WO2019147891A1 (fr)

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Cited By (3)

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CN111551745A (zh) * 2020-05-15 2020-08-18 安徽中起生物科技有限公司 禽流感病毒H7N9亚型N蛋白IgY抗体检测胶体金试纸及方法
CN112079917A (zh) * 2020-09-01 2020-12-15 武汉珈创生物技术股份有限公司 一种h7n9病毒特异性识别抗体p51h08及检测试剂盒
CN112079919A (zh) * 2020-11-06 2020-12-15 武汉珈创生物技术股份有限公司 一种h7n9病毒特异性识别抗体p52h12及检测试剂盒

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