Mutant Myxoma viruses are provided herein and methods of using these viruses to treat cancer or elicit an interferon response in a subject are also provided. The mutant Myxoma virus is modified to reduce or eliminate the activity or expression of Myxoma virus protein M62 as compared to a control virus. The mutant virus is capable of stimulating an interferon response in subjects after administration and can also lead to inhibition, reduction or elimination of the CD14+ tumor associated macrophage inhibition of CD4+ T cells in a subject having cancer and lead to a change in the tumor microenvironment to treat the cancer or work in combination with other cancer therapeutics to treat the cancer as described herein.

Provided herein are recombinant poxviruses comprising heterologous or native nucleic acids specifying excess double-stranded RNA (dsRNA) early in infection, which may further comprise heterologous nucleic acids encoding one or more costimulatory molecules, and/or heterologous nucleic acids encoding one or more infectious disease-associated antigens or tumor-associated antigens, as well as pharmaceutical compositions comprising such recombinant poxviruses and methods and uses thereof. The recombinant poxviruses provided herein enhance innate and adaptive immune activation in subjects compared to identical recombinant poxviruses lacking heterologous or native transcription units specifying excess early dsRNA.

An oncolytic poxvirus encoding a truncated human CD19 is used in conjunction with a chimeric antigen receptor to treat solid tumors.

The present document is directed to a new poxvirus infecting salmon. The present document further discloses the genomic sequence of this double-stranded DNA virus and the use of this sequence information for detection, diagnosis and/or vaccine development for the virus.

The invention provides a recombinant or synthetic or engineered or non-naturally occurring poxvirus that contains and expresses DNA encoding a heterologous or exogenous antigen, epitope or immunogen and Flagellin or an operable binding portion thereof. The poxvirus can contain or be engineered to contain and express vaccinia host range gene K1L. The poxvirus can be attenuated as to mammals, e.g., NYVAC, NYVAC.1, NYVAC.2, avipox, canarypox, fowlpox, ALVAC, TROVAC, MVA, or MVA-BN. The invention also provides methods for inducing an immunological response involving the poxvirus, and compositions containing the poxvirus. The antigen, epitope or immunogen that the poxvirus expresses can be at least one Plasmodium antigen. The Plasmodium antigen(s), epitope(s) or immunogen(s) can be SERA, ABRA, Pfhsp70, AMA-1, Pfs25, Pfs16, CSP, PfSSP2, LSA-1 repeatless, MSA-1, AMA-1 or combination(s) thereof. Advantageously the poxvirus contains DNA coding for and expresses Plasmodium antigen(s) CSP, PfSSP2, LSA-1-repeatless, MSA-1, SERA, AMA-1 and Pfs25. Also, advantageously, the poxvirus is a NYVAC poxvirus. The invention thus also provides an anti-malarial immunogenic or immunological compositions comprising the poxvirus, and methods for inducing an immunogenic or immunological response against malaria or Plasmodium in a mammal comprising administering to the mammal the poxvirus or an immunological or immunogenic composition containing the poxvirus. The mammal can be a human.

Disclosed herein, in certain embodiments, are recombinant myxoma viruses (MYXVs) and nucleic acid constructs encoding the recombinant oncolytic virus genomes and parts thereof. In some embodiments, the nucleic acid constructs include at least a portion of myxoma virus (MYXV) genome and a transgene (e.g., IL-12) driven by poxvirus P11 late promoter. The transgene is inserted at the MYXV genome to reduce or disrupt the expression of M153 gene of the MYXV genome.

Described herein is a novel method for generation of recombinant poxviruses using an E3 and K3 double deletion mutant virus as the parental virus for generation of recombinant viruses. Following allowing for crossing over between the parental virus and an insertion cassette including an orthopox K3 peptide and the gene of interest, recombinant viruses are selected by infecting a host cell line permissive for the orthopox K3 peptide but not for the E3 and K3 double mutant parental virus. It is also demonstrated that a specific small molecule inhibitor of NEDD8 activating enzyme, MLN4924, can completely block poxvirus K3 family protein mediated PKR degradation and virus replication.

The present invention relates to novel immunogenic polypeptides and their use in vaccine compositions. The invention also relates to nucleic acids, vectors and cells which express the polypeptides and the uses thereof. The polypeptides of the invention more specifically comprise an immunogenic domain and a cell membrane addressing domain which is derived from a B5R gene. The invention is particularly suited to produce vaccines for non-human animals, particularly for vaccinating swine against PCV2 infection.

Therapeutic methods for administering gut microbiota and oncolytic viruses to a subject are provided. The gut microbiota serve to pre-condition, the subject's immune system to antitumor responses and augments anticancer activity of the oncolytic vims. Combinations of the gut. microbiota and viruses and uses thereof for treating and preventing cancer are provided. The present disclosure also provides methods for building elite responder selection platforms through hierarchical clustering analysis of genomic profiles for human gut microbiome.

A method for treating a tumor by administering to a subject in need of such treatment an effective amount for treating the tumor of a Poxviridae decapping deficient mutant virus. Also disclosed are mutant Poxviridae and pharmaceutical formulations for use in the method.