The invention encompasses recombinant poxviruses, preferably modified Vaccinia Ankara (MVA) viruses, comprising a Pr13.5 promoter operably linked to a nucleotide sequence encoding an antigen and uses thereof. The invention is drawn to compositions and methods for the induction of strong CD8 T cell and antibody responses to a specific antigen(s) by administering one or more immunizations of the recombinant MVA to a mammal, preferably a human.

Provided are: a recombinant vaccinia virus which is effective for the prevention of the development of a disease by the infection by H7 avian influenza virus and has high safety; and a vaccine against H7 avian influenza virus, which comprises the recombinant vaccinia virus. The recombinant vaccinia virus according to the present invention is a recombinant vaccinia virus having such a structure that an expression promoter and the full length or a part of cDNA encoding hemagglutinin protein of H7 avian influenza virus are contained in the genome for vaccinia virus strain DIs.

The present invention is in the field of oncolytic viruses. The invention provides new poxviruses which are engineered to be defective for the function encoded by the 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. Said 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 (vaccination, especially in veterinary field). More precisely, the invention provides an alternative to the existing oncolytic viruses which are largely used in virotherapy. The m2-defective poxviruses are particularly useful for the expression of immunomodulatory polypeptides such as anti-CTLA-4 antibodies with the purposes of stimulating or improve immune response.

The disclosure relates to modified orthopoxvirus vectors, as well as methods of using the same for the treatment of various cancers. The disclosure provides modified orthopoxvirus vectors that exhibit various beneficial therapeutic activities, including enhanced oncolytic activity, spread of infection, immune evasion, tumor persistence, capacity for incorporation of exogenous DNA sequences, amenability for large scale manufacturing, and safety.

Expression vectors ideal for use in vaccinating individuals against disease based on vaccinia virus and other chordopoxviruses having high expression of recombinant genes and low expression of vector genes in target animals, and low expression of recombinant genes and high expression of vector genes in cells used for propagation.

The present disclosure relates to modified vaccinia Ankara (MVA) virus or MVAΔE3L delivered intratumorally or systemically as an anticancer immunotherapeutic agent, alone, or in combination with one or more immune checkpoint blocking agents for the treatment of malignant solid tumors. Particular embodiments relate to mobilizing the host's immune system to mount an immune response against the tumor.

This disclosure provides a modified oncolytic poxvirus, such as a vaccinia virus, that can contain modifications in the viral genome that increases production of an extracellular enveloped form of the virus. The modified oncolytic poxvirus can be utilized as a vector for systemic delivery. Also provided are methods of using the modified oncolytic poxvirus.

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.

Nucleic acid expression systems for delivery of oligonucleotides, such as RNA oligonucleotides, to target cells and methods of using the same are provided herein. Exemplary nucleic acid expression systems for expression of a payload sequence include at least one composition that delivers an inhibitor of a NF-κB pathway and/or an inhibitor of an IRF pathway. Provided herein are also pharmaceutical compositions that deliver an inhibitor of a NF-κB pathway and/or an inhibitor of an IRF pathway, and methods of using the same for enhancing expression of an oligonucleotide, such as an RNA oligonucleotide.

Provided herein are enhanced systems for potentiating cell-mediated oncolytic viral therapy. Also provided are modified viruses for such systems, and methods of treatment of cancers by administering such systems.