138 results about "Pox viruses" patented technology

The invention belongs to the technical field of immunotherapy, and particularly relates to a monkey pox virus antigen epitope peptide and application thereof. The invention aims to solve the technical problem that at present, a T cell antigen epitope peptide for universal vaccines of monkey pox viruses is not developed in the field of monkey pox viruses. According to the technical scheme of the invention, the amino acid sequence of the monkey pox virus antigen epitope peptide is shown as SEQ ID No.2. The antigen epitope peptide provided by the invention has very strong immunogenicity, and can induce antigen-specific CD8 + T cells; the antibody can be directly loaded to antigen presenting cells, can activate T cells and effectively induce T cell immunity, and can be used for research and development and preparation of universal vaccines for monkey pox viruses, research and development of drugs and clinical treatment.

The current disclosure includes a modular vaccine platform. Also included are monkeypox vaccines that protect against pathogenic monkeypox species, as well as their variants. The vaccines typically include a modified mRNA encoding at least one immunogen, such as a viral envelope protein, cell surface binding protein, or a biologically effective / significant fragment thereof. The mRNA can be encapsulated into lipid nanoparticles or other carriers and formulated as pharmaceutical compositions that can be used to generate an immune response to pathogens, including monkeypox virus, in a subject.

The invention relates to the field of biological medicine, in particular to application of Dasabuvir in preparation of orthopoxvirus inhibitors, the Dasabuvir is applied to a F13L membrane protein specific binding regulating agent and is specifically bound with palmitoylation sites on F13L membrane protein, formation of orthopoxviruses can be inhibited, the invention further provides application of the Dasabuvir in preparation of the orthopoxvirus inhibitors, the Dasabuvir is an FDA medicine, and the Dasabuvir can be applied to preparation of the orthopoxvirus inhibitors. The safety of the Dasabuvir is widely authenticated, and the Dasabuvir is successfully applied to clinical treatment, so that the Dasabuvir can be used as an effective orthopoxvirus inhibitor, the use safety can be ensured, and a new direction can be provided for inhibition of orthopoxviruses.

The invention provides a target spot for virtually screening an anti-monkey pox virus drug and application of the target spot, and belongs to the technical field of virtual screening of drugs. The target spot of the invention is a protein compound formed by molecular docking of MPXV F10 and VACV NPH-I; the amino acid sequence of the MPXV F10 is as shown in SEQ ID NO. 1, and the amino acid sequence of the VACVNPH-I is as shown in SEQ ID NO. 2. According to the invention, the crystal structure of the MPXV virus core protein F10 is determined, and a plurality of anti-monkey pox virus compounds are screened by virtual screening aiming at a contact cavity between the MPXV F10 and VACV NPH-I.

The invention discloses an SOD2 knockout cell line and application of the SOD2 knockout cell line in anti-poxvirus, and relates to the technical field of antiviral research. According to the invention, sgRNA of targeted superoxide dismutase 2 (SOD2) is designed, the sequence of the sgRNA is shown as SEQ ID NO.1-SEQ ID NO.2, then a stable SOD2 knockout human-derived non-small cell lung cancer A549 cell line is established by combining CRISPR / Cas9 gene editing with a lentiviral vector delivery technology, single-cell cloning is obtained through multiple rounds of puromycin screening, and the SOD2 gene knockout A549 cell strain is successfully constructed. Vaccinia virus Tian Tan strain infection shows that the number of plaques of SOD2 knockout cells is obviously greater than that of the plaques (about 2.3 times) of normal cell infection, and the plaques are relatively large, so that fine SOD2 has the effect of limiting intercellular transmission of poxvirus. The invention lays a foundation for research and preparation of antiviral drugs.

The invention relates to a multi-antigen monkey pox RNA vaccine and a preparation method thereof, and relates to the technical field of nucleic acid vaccines. The multi-antigen mRNA comprises a sequence encoding an antigenic polypeptide of the monkey pox virus or an antigenic fragment, variant or derivative thereof, the antigenic polypeptide or the antigenic fragment thereof comprising at least viral proteins of an intracellular mature virus and an extracellular envelope virus of the monkey pox virus. The invention provides a multi-antigen mRNA vaccine aiming at monkey pox viruses and a sequence, mRNA can express antigen protein in in-vitro cells, high-titer anti-monkey pox virus A29L, A33L, B6R, M1R and E8L protein IgG can be detected after a mouse is immunized, a high-titer anti-vaccinia Tian Tan strain live virus neutralizing antibody is generated, good immunogenicity is achieved, and the vaccine can be used for preparing the multi-antigen mRNA vaccine aiming at the monkey pox viruses. The important significance is realized on the prevention of the monkey pox virus.

Methods and compositions are described for modulating the activity of a poxvirus polymerase by modulating the assembly and / or interaction of one or more subunits of the poxvirus polymerase.

To provide oncolytic viruses, compositions and methods for delivering therapeutic polypeptides, such as checkpoint-directed antagonist antibodies for enhancing anti-tumoral adaptative immune responses in cancerous patients.SOLUTION: The invention provides new poxviruses which are engineered to be defective for a function encoded by an M2L locus (i.e., m2 function). Such poxviruses lack a functional m2 binding activity to at least one or both of CD80 and CD86 co-stimulatory antigens. The oncolytic poxviruses are preferably vaccinia virus having a total or partial deletion of the M2L locus. The present invention also relates to cells and compositions comprising such poxviruses and their use for treating proliferative diseases such as cancers and for preventing diseases.SELECTED DRAWING: None

Therapeutic polypeptides, compositions thereof and methods of use thereof for activating NK cells and treating tumors are provided. The therapeutic polypeptides can include a first domain for binding NKG2D and a second domain for binding a tumor target.

The invention discloses a novel one-pot RPA-CRISPR method for detecting monkey pox virus based on a sucrose-assisted multiphase solution system, sucrose is added in RPA reaction to increase the density of the RPA reaction, the RPA reaction is placed at the bottom of a tube, and the CRISPR reaction with lower density is kept in a water phase and located at the top of the RPA reaction; in a one-tube reaction process, newly accumulated RPA amplicons trigger non-specific cutting of Cas12a for ssDNA-FQ, so that a fluorophore is released, a real-time fluorescence signal is detected by using a fluorescence detector, and end point fluorescence can be visualized under a blue light source; compared with the prior art, the one-pot RPA-CRISPR method of the multiphase solution system is constructed by using the sucrose to increase the RPA reaction density, rapid, convenient and reliable detection of the monkey pox virus is realized, prevention and control of the monkey pox epidemic situation are facilitated, and a good example is provided for actual field detection application of the sucrose-assisted multiphase solution system.

The present invention relates to a method for producing a poxvirus viral vector-based vaccine product from a avian cell line. In some embodiments, the avian cell line is a suspended quail cell line. Pharmaceutical compositions, such as vaccines, produced by the method of the present invention are also provided. In some embodiments, the poxvirus viral vector is modified vaccinia virus ankara ("MVA") or recombinant MVA. In some embodiments, the recombinant MVA encodes a heterologous antigen and can be used to produce a vaccine against that antigen. In some embodiments, the recombinant MVA encodes an antigen of respiratory syncytial virus (RSV), and the avian cell line is used to produce a vaccine against RSV containing recombinant MVA and / or the encoded antigen.

The invention relates to the technical field of medicines, in particular to application of aspiramycin and / or imiquimod in preparation of a medicine for treating VACV. Aspiramycin and imiquimod which are screened from medicines on the market have antiviral activity, and experimental data show that the Aspiramycin and the imiquimod have anti-VACV medicine activity. Aspiramycin and imiquimod (especially combined application) are used for preparing the medicine for treating VACV, so that the time and cost of preclinical research can be greatly reduced. As the action mechanism of the pox viruses is not unique to the VACV, the combined strategy has the potential to be expanded to infection treatment of other pox viruses (such as monkey pox virus MPXV) and even other DNA (Deoxyribose Nucleic Acid) viruses.

The present invention provides a one-step multiplex fluorescence quantitative PCR kit for detecting and distinguishing poxviruses. It comprises a quantitative PCR reaction solution, an enzyme mixture, a primer-probe mixture, a standard, a positive control substance, and a negative control substance. The poxviruses include monkeypox virus, cowpox virus, and varicella virus. The present invention designs highly specific primer probes according to the highly conserved nucleotide sequences of the three poxviruses and the internal standard RNase P, and simultaneously detects and distinguishes the presence of monkeypox virus, cowpox virus, and varicella virus from samples such as blood, follicle fluid, and rash swabs through a PCR reaction, and uses RNase P as the internal standard for evaluating the amplification system, which is simpler, faster, and less costly than the single-plex fluorescence quantitative PCR method, and has better sensitivity, specificity, and repeatability. The viruses to be tested are fully enclosed for detection and single-tube real-time quantification, and the three poxviruses can be efficiently and quickly screened and identified according to the number of copies of the virus infection.

The invention discloses an application of diphyllin in preparation of drugs for inhibiting poxvirus and preventing or treating poxvirus infection, the poxvirus is common orthopoxvirus poxvirus, the poxvirus comprises vaccinia virus (VACV), vaccinia virus (CPXV) and rabbit poxvirus mucinoma virus (MYXV), the content of diphyllin is in a range of 1.25-2.5 [mu] M / mL, and the content of diphyllin is in a range of 1.25-2.5 [mu] M / mL. The compound has a remarkable inhibiting effect on infection of poxvirus family members such as CPXV, is expected to be used as a medicine for preventing and treating infection of CPXV and other poxviruses, and has important significance on prevention and control of diseases related to poxvirus infection.

The present invention relates to a mammalian non-human cell line, specifically a Chinese hamster ovary (CHO) cell line, in which the genes are modified to express CP77, K1L and / or SPI-1, which are host range genes of poxviruses not expressed by MVA, and to the use of such cell lines in the replication of MVA.

The present application relates to a kind of recombinant vaccinia virus and its use, which is deleted at least one of TK gene, F4L gene and B2R gene relative to vaccinia virus Tianlu strain.The recombinant vaccinia virus of the present application has the characteristics of low toxicity, can be completely replicated and has higher immunogenicity.Therefore, the recombinant vaccinia virus provided by the present application has higher safety and enhanced immunogenicity.The recombinant vaccinia virus provided by the present application has higher application value as vaccine, can be used for preventing the infection of poxviridae virus, and as virus vector for constructing other infectious disease vaccine and tumor vaccine etc..

The invention belongs to the technical field of biology, and discloses an anti-monkey pox virus E8 antibody or an antigen binding fragment thereof and application thereof. The invention provides an anti-monkey pox virus E8 monoclonal antibody 2F6, 9G4, 9H1 or 10E11, which can specifically recognize and target orthopox viruses such as monkey pox, vaccinia and the like, and shows efficient virus neutralizing capacity. The clinical application value of preventing and treating orthopoxvirus infection is realized; the compound can be used for detecting orthopoxvirus, diagnosing diseases related to orthopoxvirus infection and preventing and / or treating orthopoxvirus infection and / or diseases related to orthopoxvirus infection.

The present invention generally relates to a method for designing recombinant poxviruses for therapeutic vaccines, i.e., personalized cancer vaccines, wherein the recombinant poxviruses comprise one or more expression cassettes, each expressing a fusion of multiple peptides (i.e., neopeptides), the method comprising performing, by a processing means (11) of a server (1), the following steps: (a) selecting a first subset of candidate peptides, wherein the candidate peptides exhibit a membrane-spanning score below a TMS threshold; (b) determining an optimal distribution of the candidate peptides from the first subset into one or more expression cassettes from among a plurality of possible distributions, wherein, if more than one expression cassette is present, the optimal distribution exhibits the lowest range of hydropathic scores of the two or more expression cassettes; (c) determining, for each expression cassette, an optimal slot assignment of the candidate peptides as a function of the cassette's slot occupancy rules, in order to select the peptide fusion with the lowest TM score; and (d) determining a DNA transfer sequence comprising the nucleotide sequence of the one or more expression cassettes to generate the recombinant poxvirus.

The utility model provides a disposable throat swab specimen preservation tube, and relates to the field of specimen preservation. The disposable throat swab specimen preservation tube comprises a plastic tube, the outer side of the plastic tube is fixedly sleeved with a limiting ring, two arc-shaped inner grooves are formed in the limiting ring, two arc-shaped inserting grooves are formed in the top of the limiting ring, and a sealing film is fixedly connected to the interior of the plastic tube. The disposable throat swab specimen preservation tube is simple in structure and low in cost, the plastic tube, the outer threaded tube, the transparent plate, the inner threaded tube, the plastic slender rod, the sealing film, the limiting ring and the like are all made of degradable materials and are discarded after being used, the internal condition of the plastic tube can be observed through the transparent plate, and the disposable throat swab specimen preservation tube is convenient to use. When the interior of the plastic pipe has an obvious characteristic of deterioration, the plastic pipe and a monkey pox virus sample in the plastic pipe can be directly discarded, so that the situation that deterioration can be found only after the transparent plate and the inner threaded pipe are opened is avoided.

The invention provides a 2-deoxy-2-fluoro-beta-D-furan nucleoside derivative as well as a preparation method and application of the 2-deoxy-2-fluoro-beta-D-furan nucleoside derivative. The derivative has a structure as shown in I or II. The invention also relates to a preparation method of the compound and application of the compound as an anti-poxvirus inhibitor in preparation of anti-poxvirus drugs.

The present invention relates to recombinant poxvirus, such as recombinant Modified Vaccina Virus Ankara (MVA), encoding a fusion protein comprising a disease-associated antigen that is joined to a subunit of a self-assembling protein nanoparticle, and to medical uses thereof.

Provided are a poxvirus mRNA vaccine and a use. Specifically, provided is an isolated mRNA molecule, comprising a coding region, the coding region coding a target protein, and the target protein comprising the following four proteins: vaccinia virus surface antigens A27, L1, A33, and B5, wherein every two adjacent proteins are independently directly linked or linked by identical or different linkers. Animal immunization results show that the mRNA molecule has good candidate vaccine potential and provides an innovative idea for the development of poxvirus vaccines.

The present invention relates to monoclonal antibodies or antigen-binding portion thereof that have neutralizing or cross-neutralizing activity against poxvirus, in particular against monkeypox virus, vaccinia virus and cowpox virus. The invention relates also to the use of such monoclonal antibodies or antigen binding portion thereof in therapy, prophylaxis and diagnosis of poxvirus, in particular monkeypox virus, vaccinia virus and cowpox virus dependent diseases.

The present disclosure provides pharmaceutical compositions for delivery of orthopoxvirus antigens (e.g., mpox, variola, borealpox, ectromelia, cowpox, volepox, modified vaccinia virus Ankara, or vaccinia) and related technologies (e.g., components thereof and / or methods relating thereto). For example, the present disclosure provides polyribonucleotides encoding one or more mpox antigens, fragments, or fusions thereof.

The present invention relates to a mammalian non-human cell line, in particular a Chinese hamster ovary (CHO) cell, genetically modified to express poxvirus host range genes CP77, K1L and / or SPI-1, which are not expressed in MVA, and to the use of said cell line in MVA propagation.

The invention provides an anti-orthopoxvirus monoclonal antibody and application thereof, the monoclonal antibody is obtained by screening through a flow cytometry sorting technology and a single cell PCR technology, has a unique CDR partition, and is mainly used for recognizing L1R (M1R) antigen protein of orthopoxvirus. The affinity of the antibody to VARV (Vector Activated Receptor Virus), VACV (Vector Activated Receptor Virus), CPXV (Cytopoxvirus) and MPXV (Metapoxvirus) of orthopoxvirus is 1.84 nM, 1.46 nM, 2.71 nM and 2.57 nM respectively. In a virus neutralization experiment, the IC50 of the antibody and mature virions in vaccinia virus cells is 37.93 pM. In a monkey pox virus infected mouse model, the antibody can treat a monkey pox virus infected mouse. The monoclonal antibody disclosed by the invention has the characteristics of high expression, high neutralizing activity and good broad spectrum, can be used for industrial production, and can be applied to coping with orthopoxvirus infection outbreak possibly occurring in the future.

The present invention relates to methods of producing poxvirus viral vector-based vaccine products from avian cell lines. In some embodiments, the avian cells are suspension quail cell lines. Pharmaceutical compositions such as vaccines produced by the methods of the invention are also provided. In some embodiments, the poxvirus viral vector is Modified Vaccinia Virus Ankara (“MVA”) or recombinant MVA. In some embodiments, the recombinant MVA encodes heterologous antigens and can be used to produce a vaccine against the antigens. In some embodiments, the recombinant MVA encodes antigens of Respiratory Syncytial Virus (RSV) and the avian cells are used to produce a vaccine against RSV comprising the recombinant MVA and / or the encoded antigens.

The application provides application of Gidalizie in preparation of an anti-monkeypox virus drug, and proves that the multi-target inhibitor Gidalizie can effectively inhibit replication of the monkeypox virus at a low-toxicity concentration through in-vitro experiments, reveals a new use of Gidalizie as an anti-monkeypox virus drug, and provides an important basis and a candidate compound for development of a new, safe and effective monkeypox treatment drug.

The present application provides compositions of induced pluripotent stem cells (iPSCs) or pancreatic beta cells and poxviruses, as well as methods of making the compositions and methods of using the compositions to treat diseases.