Methods of producing a pathogen with reduced replicative fitness are disclosed, as are attenuated pathogens produced using the methods. In particular examples, the method includes deoptimizing one or more codons in a coding sequence, thereby reducing the replicative fitness of the pathogen. Methods of using the attenuated pathogens as immunogenic compositions are also disclosed.

Disclosed herein are high transducing replication defective herpes simplex virus (HSV) vectors of McKrae strain.

The present disclosure relates to recombinant viral vectors for the treatment and prevention of cancer. Oncolytic viral vectors incorporate one or more of the following features: viral replication restriction by insertion of tumor-suppressive microRNA (miRNA) target sequences into the viral genome; disruption of oncogenic miRNA function; cancer microenvironment remodeling; and cancer cell targeting by incorporation of protease-activated antibodies into the viral particle.

The present invention provides vaccines for treating or preventing a herpes simplex virus infection and methods of using and making the vaccine. Further provided are recombinant herpes simplex virus genomes, recombinant viruses, and immunogenic compositions.

The present invention provides a recombinant herpes simplex virus (HSV), comprising (a) a mutation of the glycoprotein B (gB) at position 285 or 549, (b) a plurality of copies of one or more microRNA target sequences inserted into a locus of an HSV gene required for HSV replication, wherein said target sequence is the reverse complement of microRNA miR-124 and wherein said target sequence is present in the ICP4 gene, and (c) a transgene encoding a matrix metalloproteinase. The present invention also provides a method of killing a cancerous cell using a recombinant HSV according to the invention and a pharmaceutical composition comprising a pharmaceutically acceptable carrier and a recombinant HSV according to the invention.

Recombinant herpes simplex virus 2 (HSV-2) vaccine vectors, virions thereof, compositions and vaccines comprising such, and methods of use thereof are each provided.

The present invention provides a recombinant oncolytic Herpes Simplex Virus (oHSV) comprising a non-HSV ligand specific for a molecule (protein, lipid, or carbohydrate determinant) present on the surface of a cell (such as a cancer cell) and one or more copies of one or more microRNA target sequences inserted into one or more HSV gene loci, preferably one or more HSV gene(s) required for replication of HSV in normal (i.e., non-cancerous) cells. The invention further provides stocks and pharmaceutical compositions comprising the inventive oHSV and methods for killing tumor cells employing the inventive oHSV.

The present disclosure provides recombinant nucleic acids comprising one or more polynucleotides encoding an immunomodulatory polypeptide (e.g., a pro-inflammatory cytokine such as a human IL-2 or IL-12 polypeptide); viruses comprising the recombinant nucleic acids; compositions and formulations comprising the recombinant nucleic acids and/or viruses; methods of their use (e.g., for the treatment of cancer, such as lung cancer); and articles of manufacture or kits thereof.

Nucleic acid molecules comprising a coding sequence with at least one codon substituted to a synonymous codon, a modified form of a virus comprising the nucleic acid molecules of the invention, and methods for producing these nucleic acid molecules, and viruses, are provided.

The present invention provides a recombinant herpes simplex virus (HSV), comprising (a) a mutation of the glycoprotein B (gB) at position 285 or 549, (b) a plurality of copies of one or more microRNA target sequences inserted into a locus of an HSV gene required for HSV replication, wherein said target sequence is the reverse complement of microRNA miR-124 and wherein said target sequence is present in the ICP4 gene, and (c) a transgene encoding a matrix metalloproteinase. The present invention also provides a method of killing a cancerous cell using a recombinant HSV according to the invention and a pharmaceutical composition comprising a pharmaceutically acceptable carrier and a recombinant HSV according to the invention.