43 results about "Vaccinia viruses" patented technology

The present invention relates to oncolytic vaccinia viruses which have been modified to promote anti-tumor immunity and / or reduce host immunity and / or antibody response against the virus. It is based, at least in part, on the discovery that oncolytic vaccinia virus (i) bearing a genome deletion of a gene that reduces T cell immunity (interleukin-18 binding protein); (ii) treated with a sialidase enzyme which is believed to reduce TLR2 activation and therefore the antibody response; (iii) carrying a gene that enhances cytotoxic T lymphocyte induction (e.g., TRIF) and / or (iv) reduces tumor myeloid-derived suppressor cells by reducing prostaglandin E2 reduces tumor growth. Accordingly, the present invention provides for immunooncolytic vaccinia viruses and methods of using them in the treatment of cancers.

The present invention relates to recombinant vaccinia viruses derived from the modified vaccinia virus Ankara (MVA) and containing and capable of expressing foreign genes which are inserted at the site of a naturally occurring deletion in the MVA genome, and the use of such recombinant MVA viruses for the production of polypeptides, e.g. antigens or therapeutic agents, or viral vectors for gene therapy, and the use of such recombinant MVA viruses encoding antigens as vaccines.

The present invention relates to novel vaccines against malaria infections, based on recombinant viral vectors, such as alpha viruses, adenoviruses or vaccinia viruses. The recombinant viral-based vaccines can be used to immunize against different Plasmodium infections, such as infections by P. falciparum or P. yoelii. Novel codon-optimized circumsporozoite genes are disclosed. Preferably, replication-defective adenoviruses are used, derived from serotypes that encounter low titers of neutralizing antibodies. The invention, therefore, also relates to the use of different adenoviral serotypes that are administered to elicit a strong immune response, either in single vaccination set-ups or in prime-boost set-ups in which compositions based on different serotypes can be applied.

Attenuated, replication-deficient viruses such as vaccinia viruses are used to deliver an exogenous viral, bacterial, parasitic or tumor antigen to an epidermal tissue such as the skin, lungs or gastrointestinal tract, which has been mechanically disrupted, in an amount effective to elicit or stimulate a cell mediated immune response. The epidermal tissue may be mechanically disrupted by a device such as a scarification needle or an abrader device. The epidermis may be mechanically disrupted prior to, at the same time, or immediately after the administration of the vaccine. The vaccine can be used to induce immunity against a pathogen, such as a virus, bacteria, or parasite, or against a cancer in a subject that has or is at risk of developing cancer. In some embodiments a co-stimulatory molecule, a growth factor, an adjuvant and / or a cytokine is administered before, with or after the viral vaccine. In some embodiments, the co-stimulatory molecule is co-expressed with the antigen by the virus.

The present invention relates to methods for purification of Vaccinia viruses (VV) and / or Vaccinia virus (VV) particles, which can lead to highly pure and stable virus preparations of predominantly biologically active viruses. The invention encompasses purifying a virus preparation in a sterilized way with high efficiency and desirable yield in terms of purity, biological activity and stability, aspects advantageous for industrial production.

The present invention relates to vaccines having an increased level of safety comprising recombinant vaccinia viruses containing an inactivated E3L region. The invention also relates to methods for stimulating a protective immune response in an immunized host using the vaccines of the invention. The invention is based on the discovery that vaccinia virus mutants having deletions in the E3L region exhibit dramatically reduced pathogenesis while remaining highly immunogenic. In addition, the invention relates to modified recombinant vaccinia viruses engineered to express heterologous polypeptides and the use of such viruses in vaccines designed to stimulate a protective immune response against such polypeptides in a host. The invention further relates to an interferon-sensitive recombinant vaccinia virus with broad host range wherein a salamander eIF2α is inserted into the viral genome in place of at least a portion of the E3L gene.

The present invention relates to vaccines having an increased level of safety comprising recombinant vaccinia viruses. The invention also relates to methods for stimulating a protective immune response in an immunized host using the vaccines of the invention. The vaccines and recombinant vaccinia viruses of the invention comprise a first nucleic acid comprising an expression control sequence and a second nucleic acid comprising an exogenous nucleic acid encoding a conditional replication gene product, wherein the expression control sequence is operably linked to the exogenous nucleic acid. The exogenous nucleic acid may, by its expression or non-expression, confer upon the recombinant vaccinia virus either sensitivity or dependence upon an exogenous molecule (e.g. a drug) or a condition. Importantly, to allow the recombinant vaccinia viruses of the invention to replicate normally under permissive conditions, the exogenous nucleic acid is inserted into a non-essential locus, e.g., the E2L / E3L inter-genic locus, K1L / K2L inter-genic locus, the superoxide dismutate locus, and the 7.5 K locus.

The present invention relates to methods for purification of Vaccinia viruses (VV) and / or Vaccinia virus (VV) particles, which can lead to highly pure and stable virus preparations of predominantly biologically active viruses. The invention encompasses purifying a virus preparation in a sterilized way with high efficiency and desirable yield in terms of purity, biological activity and stability, aspects advantageous for industrial production.

The present invention relates to methods for purification of Vaccinia viruses (VV) and / or Vaccinia virus (VV) particles, which can lead to highly pure and stable virus preparations of predominantly biologically active viruses. The invention encompasses purifying a virus preparation in a sterilized way with high efficiency and desirable yield in terms of purity, biological activity and stability, aspects advantageous for industrial production.

The invention discloses N-indazole substituted thiourea derivatives and a preparation method and application thereof and belongs to the technical field of chemical medicine.The thiourea derivatives are a series of compounds simultaneously containing the 1H-indazole ring structure and the asymmetrical thiourea structure, and the compounds are not reported in the literature.The bioactivity test result analysis of the thiourea derivatives show that the compounds are good in antioxidant activity, the average scavenging rate is above 80%, the scavenging rate of the compound 12b, the compound 12c, and the compound 12d and the compound 12h is higher than 90%, the scavenging activity IC50 of the compound 12h on DPPH is 0.14mg / mL; part of the target compounds has certain inhibition activity on herpes viruses, vaccinia viruses, reoviruses, Coxsackie viruses, Feline coronary herpes viruses, HIV viruses and the like, and the compound 12c and the compound 12n are high in antivirus activity; the synthesized compounds hopefully have new bioactivity which is not expounded, and a certain material basis is provided for the development of new medicine.

The present invention relates to methods for purification of Vaccinia viruses (W) and / or Vaccinia virus (W) particles, which can lead to highly pure and stable virus preparations of predominantly biologically active viruses. The invention encompasses purifying a virus preparation in a sterilized way with high efficiency and desirable yield in terms of purity, biological activity and stability, aspects advantageous for industrial production.

The present invention relates to methods for purification of Vaccinia viruses (W) and / or Vaccinia virus (W) particles, which can lead to highly pure and stable virus preparations of predominantly biologically active viruses. The invention encompasses purifying a virus preparation in a sterilized way with high efficiency and desirable yield in terms of purity, biological activity and stability, aspects advantageous for industrial production.

The present invention discloses recombinant vaccinia virus (VV) virions that are resistant to antiviral defenses and have enhanced anti-tumor activities. In one embodiment, the recombinant VV comprise one or more variant VV proteins that have mutations at one or more neutralizing antibody epitopes, thereby conferring viral escape from the neutralizing antibodies. In another embodiment, the recombinant VV is resistant to complement-mediated neutralization due to the expression of a regulator of complement activation (e.g. CD55). In another embodiment, the recombinant VV has enhanced anti-tumor activities due to the expression of bi-specific antibodies co-targeting cancer cells and immune effector cells, or the expression of a polypeptide blocking the PD-1 pathway. The recombinant vaccinia virus virions can be used to treat cancer in a subject.

The present invention relates generally to the fields of oncology, virology and immunotherapy. More particularly, it concerns the use of poxviruses, specifically the replication competent attenuated vaccinia virus with deletion of thymidine kinase (VC-TK−) with and without the expression of human Flt3L or GM-CSF as oncolytic and immunotherapy. The foregoing poxviruses can also be used in combination with immune checkpoint blocking agents. The foregoing poxviruses can also be inactivated via Heat or UV-treatment and the inactivated virus can be used as immunotherapy either alone or in combination with immune checkpoint blocking agents.

The present disclosure pertains to a compositions and combinations for simultaneous, separate or sequential use which comprises (a) an oncolytic vaccinia virus that expresses a cytokine and a carboxylesterase enzyme, and, preferably, (b) a cancer co-drug, and to their uses for the treatment of cancer.

The present invention relates to oncolytic vaccinia viruses which have been modified to promote anti-tumor immunity and / or reduce host immunity and / or antibody response against the virus. It is based, at least in part, on the discovery that oncolytic vaccinia virus (i) bearing a genome deletion of a gene that reduces T cell immunity (interleukin-18 binding protein); (ii) treated with a sialidase enzyme which is believed to reduce TLR2 activation and therefore the antibody response; (iii) carrying a gene that enhances cytotoxic T lymphocyte induction (e.g., TRIF) and / or (iv) reduces tumor myeloid-derived suppressor cells by reducing prostaglandin E2 reduces tumor growth. Accordingly, the present invention provides for immunooncolytic vaccinia viruses and methods of using them in the treatment of cancers.