343 results about "Neuraminidase" patented technology

Polypeptides, polynucleotides, methods, compositions, and vaccines comprising influenza hemagglutinin and neuraminidase variants are provided.

The present invention is based on the development of a dual promoter system (preferably a RNA pol I-pol II system) for the efficient intracellular synthesis of viral RNA. The resultant minimal plasmid-based system may be used to synthesize any RNA virus, preferably viruses with a negative single stranded RNA genome. The viral product of the system is produced when the plasmids of the system are introduced into a suitable host cell. One application of the system is production of attenuated, reassortant influenza viruses for use as antigens in vaccines. The reassortant viruses generated by cotransfection of plasmids may comprise genes encoding the surface glycoproteins hemagglutinin and neuramimidase from an influenza virus currently infecting the population and the internal genes from an attenuated influenza virus. An advantageous property of the present invention is its versatility; the system may be quickly and easily adapted to synthesize an attenuated version of any RNA virus. Attenuated or inactivated RNA viruses produced by the present invention may be administered to a patient in need of vaccination by any of several routes including intranasally or intramuscularly.

A method of altering the targeting and / or cellular uptake efficiency of an adeno-associated virus (AAV) viral vector having a capsid containing an AAV9 cell surface binding domain is described. The method involves modifying a clade F cell surface receptor which comprises a glycan having a terminal sialic acid residue and a penultimate β-galactose residue. The modification may involve retargeting the vector by temporarily functionally ablate AAV9 binding in a subset of cells, thereby redirecting the vector to another subset of cells. Alternatively, the modification may involve increasing cellular update efficiency by treating the cells with a neuraminidase to expose cell surface β-galactose. Also provided are compositions containing the AAV9 vector and a neuraminidase. Also provided is a method for purifying AAV9 using β-galactose linked to solid support. Also provided are mutant vectors which have been modified to alter their targeting specificity, including mutant AAV9 in which the galactose binding domain is mutated and AAV in which an AAV9 galactose binding domain is engineered.

An anti-influenza vaccine composition wherein the improvement is that the vaccine includes, as an additive, neuraminidase (NA). The base anti-influenza vaccine can be any commercially available anti-influenza vaccine. The composition can include and be administered with an adjuvant. The vaccine composition provides protection in a host, animal or human, against influenza infection, including viral replication and systemic infection. Oral, nasal or other mucosal or per needle administration, including intracutaneous, intradermal, intramuscular, intravascular, and intravenous, are included.

The present invention is based on the development of a dual promoter system (preferably a RNA pol I-pol II system) for the efficient intracellular synthesis of viral RNA. The resultant minimal plasmid-based system may be used to synthesize any RNA virus, preferably viruses with a negative single stranded RNA genome. The viral product of the system is produced when the plasmids of the system are introduced into a suitable host cell. One application of the system is production of attenuated, reassortant influenza viruses for use as antigens in vaccines. The reassortant viruses generated by cotransfection of plasmids may comprise genes encoding the surface glycoproteins hemagglutinin and neuraminidase from an influenza virus currently infecting the population and the internal genes from an attenuated influenza virus. An advantageous property of the present invention is its versatility; the system may be quickly and easily adapted to synthesize an attenuated version of any RNA virus. Attenuated or inactivated RNA viruses produced by the present invention may be administered to a patient in need of vaccination by any of several routes including intranasally or intramuscularly.

Polypeptides, polynucleotides, methods, compositions, and vaccines comprising influenza hemagglutinin and neuraminidase variants are provided.

Described herein are vaccines and the use of naked DNA and / or RNA encoding hemagglutinin (HA) from pandemic influenza, e.g., the 1918 H1N1 and / or the 1957 H2N2 and / or the 1968 H3N2 influenza A virus, as a vaccine component against present day and coming H1, H2, H3, H5, N1, N2 containing influenza A infections in humans and swine optionally with the naked DNA and / or RNA encoding Neuraminidase (NA) and / or matrix protein (M) and / or the nucleoprotein (NP) from pandemic influenza virus included. If the vaccine components are used as DNA or RNA vaccines with or without the corresponding protein, the codons can optionally be “humanized” using preferred codons from highly expressed mammalian genes and the administration of this DNA vaccine can be by saline or buffered saline injection of naked DNA or RNA, or injection of DNA plasmid or linear gene expressing DNA fragments coupled to particles. Addition of the matrix protein (M) and / or the nucleoprotein (NP) from the 1918 influenza strain is also disclosed.

The present invention provides a vaccine, method of use, and kit employing genetically isolated and stabilized, live attenuated bacterial strains including Salmonella that express one or more avian influenza antigens for use in live vaccine compositions that can be orally administered to an individual to protect against avian influenza. Genetic stabilization may be achieved through deletion of IS200 elements and bacteria phage and prophage elements. The bacterial strains may be genetically isolated from external phage infection by constitutive expression of a P22 phage repressor. Nucleic acid sequences encoding antigenic hemagglutinin and neuraminidase avian influenza proteins, having at least one modified codon for optimum expression when transferred into a prokaryotic microorganism for improved immunogenicity

Compounds I-III wherein U is CH, O, or S; Z is mono- or di-substituted carbon; R is (CH2)nCO2H, (CH2)nSO3H, (CH2)nPO3H2, (CH2)nNO2, CH(SCH3)3, esters; R1 is H, hydroxyalkyl, aminoalkyl, alkoxyalkyl; RR1 is O; n is 0-4; R2, R3 is H, hydroxyalkyl, aminoalkyl, alkoxyalkyl, haloalkyl; R4 is (CH2)nOH, (CH2)nNH2, substituted alkyl were prepd. as neuraminidase inhibitors. Thus, (1R,3R,4R,1'S)-(-)-(1'-acetylamino-2 '-ethyl)butyl-4-(aminoimino)methylaminocyclopentan-1-carboxylic acid was prepd. and tested in vitro as neuraminidase inhibitor (IC50<1.mu.M).

The present invention relates to the intersection of the fields of immunology and protein engineering, and particularly to antigens and vaccines useful in prevention of infection by influenza virus. Provided are recombinant protein antigens, compositions, and methods for the production and use of such antigens and subunit vaccine compositions. In some embodiments, influenza antigens include hemagglutinin polypeptides neuraminidase polypeptides, and / or combinations thereof.

Glycan arrays that can detect and distinguish between various sub-types and strains of influenza virus are provided. Methods for using the glycan arrays with assays using nanoparticle amplification technique are disclosed. Sandwich assays using gold nanoparticles conjugated to phage particles comprising influenza virus-specific antibodies for detecting multiple serotypes using a single reaction are provided. Plurality of glycans directed to specific target HA of influenza virus comprises the array. Detector molecules comprising noble metals conjugated to (a) phage display particles expressing antibodies against hemagglutinin and (b) neuraminidase binding agents are disclosed.

A sensor for the detection of tetrameric multivalent neuraminidase within a sample is disclosed, where a positive detection indicates the presence of a target virus within the sample. Also disclosed is a trifunctional composition of matter including a trifunctional linker moiety with groups bonded thereto including (a) an alkyl chain adapted for attachment to a substrate, (b) a fluorescent moiety capable of generating a fluorescent signal, and (c) a recognition moiety having a spacer group of a defined length thereon, the recognition moiety capable of binding with tetrameric multivalent neuraminidase.

The present invention relates to reagents and methods for influenza virus detection. These reagents and methods disclosed in the present invention enable simple, rapid, specific and sensitive detection of influenza virus types A and B. These reagents are N-acetylneuraminic acid-firefly luciferin conjugates which can be cleaved by influenza virus neuraminidase.

The present invention relates to targets for Human microRNAs in Avian Influenza Virus (H5N1) Genome and provides specific miRNA targets against H5N1 virus. Existing therapies for Avian flu are of limited use primarily due to genetic re-assortment of the viral genome, generating novel proteins, and thus escaping immune response. In animal models, baculovirus-derived recombinant H5 vaccines were immunogenic and protective, but results in humans were disappointing even when using high doses. Currently, two classes of drugs are available with antiviral activity against influenza viruses: inhibitors of the M2 ion channel, amantadine and rimantadine, and inhibitors of neuraminidase, oseltamivir, and zanamivir. There is paucity of information regarding effectiveness of these drugs in H5N1 infection. These drugs are also well known to have side effects like neurotoxicity. Thus there exists a need to develop alternate therapy for targeting the Avian flu virus (H5N1). The present invention addresses this need in the field.

Polypeptides, polynucleotides, methods, compositions, and vaccines comprising influenza hemagglutinin and neuraminidase variants are provided.

Polypeptides, polynucleotides, methods, compositions, and vaccines comprising influenza hemagglutinin and neuraminidase variants are provided.

A method for manufacturing recombinant neuraminidase by culturing in a suitable culture medium host cells which are transformed with a neuraminidase expression vector or infected with a virus which is transformed with a neuraminidase expression vector, wherein the expression vector comprises at least a part of the coding region of a neuraminidase gene of an influenza virus minus the region which codes for the membrane anchor, or a modified version thereof, preceded in phase by a signal sequence; and isolating the expression product neuraminidase from the culture medium. The invention further relates to vectors expressing the neuraminidase.

An aspect of the present invention is directed towards DNA plasmid vaccines capable of generating in a mammal an immune response against a plurality of influenza virus subtypes, comprising a DNA plasmid and a pharmaceutically acceptable excipient. The DNA plasmid is capable of expressing a consensus influenza antigen in a cell of the mammal in a quantity effective to elicit an immune response in the mammal, wherein the consensus influenza antigen comprises consensus hemagglutinin (HA), neuraminidase (NA), matrix protein, nucleoprotein, M2 ectodomain-nucleo-protein (M2e-NP), or a combination thereof. Preferably the consensus influenza antigen comprises HA, NA, M2e-NP, or a combination thereof. The DNA plasmid comprises a promoter operably linked to a coding sequence that encodes the consensus influenza antigen. Additionally, an aspect of the present invention includes methods of eliciting an immune response against a plurality of influenza virus subtypes in a mammal using the DNA plasmid vaccines provided.

Polypeptides, polynucleotides, methods, compositions, and vaccines comprising (avian pandemic) influenza hemagglutinin and neuraminidase variants are provided.

Methods for producing reassortant viruses are provided wherein the transcription and / or translation of the hemagglutinin and / or neuraminidase genes are suppressed.

Polypeptides, polynucleotides, methods, compositions, and vaccines comprising (avian pandemic) influenza hemagglutinin and neuraminidase variants are provided.

The invention relates to a double reagent, in particular to a liquid double reagent for determining sialic acid by an enzyme method and application thereof. The technical proposal of the liquid double reagent comprises: the steady liquid double reagent for determining the sialic acid by the enzyme method consists of a reagent 1 and a reagent 2, wherein the reagent 1 comprises 0.01 to 50KU / L of neuraminidase, 0.1 to 50KU / L of lactate dehydrogenase, and 25 to 100mmol / L of buffer liquid; and the reagent 2 comprises 0.1 to 50KU / L of N-acetyleuraminic acid aldolase, 0.05 to 5mmol / L of reducing coenzyme NADH, 0.1 to 10000U / L of glucose dehydrogenase, 0.1 to 500mmol / L of glucose, and 5 to 100mmol / L of the buffer liquid. The liquid double reagent has the advantages that the liquid double reagent has convenient use, does not need a dissolving solution to redissolve, has small difference among bottles, ensures that the packaging of the liquid double reagent can adapt to various automatic biochemical analyzers, can avoid secondary pollution, and simplify a production technology method.

The invention relates to a method and a kit for stably detecting sialic acid by an enzyme method. The method comprises the following steps of: generating N-acetylneuraminic acid from bound sialic acid under the catalysis of neuraminic acid aldolase; transforming the N-acetylneuraminic acid into N-acetylmannosamine under the catalysis of neuraminidase; reacting the product with mannosamine dehydrogenase and nicotinamide adenine dinucleotide (NAD) to generate reduced nicotinamide adenine dinucleotide (NADH); and measuring the sialic acid content by detecting the amount of the generated NADH. The invention also relates to the kit prepared according to the method. The method and the kit are conveniently and quickly used, the sialic acid is not required to be redissolved by dissolving liquid, is stable for a long time and has small inter-bottle variation, the method and the kit are suitable for various biochemical analyzers, secondary pollution is avoided, and a production process method is simplified.

The invention provides a compound expressed by a general formula I, or its pharmaceutically acceptable salt, and an analyzed enantiomer and a purified diastereomer, wherein R<1>is H or C1-12 alkyl groups; R<2> is H, -C(O)R<1a>, -C(O)OR<1a> or -S(O)2R<1b>, wherein R<1a> is H or C1-6 alkyl groups, R<1b> is selected from H or C1-6 alkyl groups halogenated hydrocarbon, phenyl or aryl group; R<3> is selected from C1-4 alkyl groups substituted amino, halogen, hydroxyl, sulfydryl, guanidyl, nitryl or cyano group; and R<4> is -(CH2)nCO2H, -(CH2)nP(O)(OH)2, -(CH2)nCO2R<1a> and -(CH2)nP(O)(OR<1a>)2, wherein R<1a> is H or C1-6 alkyl groups, n is an integer between 0 and 4, or a salt of the above groups. The invention also provides a preparation method of the cyclohexene compound expressed by the general formula I, and an application of the cyclohexene compound taken as an influenza virus neuraminidase inhibitor for preparing the medicines to prevent or treat the influenza diseases.

The present invention discloses that an intratumoral injection of: i) glycolipids with α-gal epitope; ii) gene vectors comprising an α1,3galactosyltransferase gene; or iii) a mixture of α1,3galactosyltransferase, neuraminidase, and uridine diphosphate galactose results in tumor regression and / or destruction. Binding of the natural anti-Gal antibody to de novo expressed tumoral α-gal epitopes induces inflammation resulting in an anti-Gal antibody mediated opsonization of tumor cells and their uptake by antigen presenting cells. These antigen presenting cells migrate to draining lymph nodes and activate tumor specific T cells thereby converting the treated tumor lesions into in situ autologous tumor vaccines. This therapy can be applied to patients with multiple lesions and in neo-adjuvant therapy to patients before tumor resection. In addition to the regression and / or destruction of the treated tumor, such a vaccine will help in the immune mediated destruction of micrometastases that are not detectable during the removal of the treated tumor.