The invention relates to vectors comprising two or more homologous nucleotide sequences and methods for generating them. The invention concerns substituting bases in the homologous nucleotide sequences with different bases that do not alter the encoded amino acid sequence. The invention allows for the reduction of intramolecular recombination between homologous nucleotide sequences, in particular in mammalian cells. The invention further relates to nucleotide sequences containing substituted bases.

The present invention provides vectors that contain and co-express in vivo or in vitro immunogenic polypeptides or antigens together with an OX40L polypeptide, which functions as a genetic adjuvant. Together, the immunogenic polypeptide and the OX40L polypeptide elicit an immune response in animal or human, which is greater than the immune response elicited by the immunogenic polypeptide alone. In a particular example, the invention provides vectors encoding a Rabies G immunogenic polypeptide and a canine OX40L genetic adjuvant, which vectors elicit strong immune responses in canine against rabies virus.

The compositions and methods are described for generating an immune response to a hemorrhagic fever virus such as ebolavirus, Marburgvirus, or arenavirus. The compositions and methods described herein relate to a modified vaccinia Ankara (MVA) vector encoding one or more viral antigens for generating a protective immune response to a member of genus Ebolavirus (such as a member of species Zaire ebolavirus), a member of genus Marburgvirus (such as a member of species Marburg marburgvirus), or a member of genus Arenavirus (such as a member of species Lassa virus) in the subject to which the vector is administered. The compositions and methods of the present invention are useful both prophylactically and therapeutically and may be used to prevent and/or treat an infection caused by ebolavirus, Marburgvirus, or arenavirus.

The compositions and methods are described for generating an immune response to a hemorrhagic fever virus such as ebolavirus, Marburgvirus, or arenavirus. The compositions and methods described herein relate to a modified vaccinia Ankara (MVA) vector encoding one or more viral antigens for generating a protective immune response to a member of genus Ebolavirus (such as a member of species Zaire ebolavirus), a member of genus Marburgvirus (such as a member of species Marburg marburgvirus), or a member of genus Arenavirus (such as a member of species Lassa virus) in the subject to which the vector is administered. The compositions and methods of the present invention are useful both prophylactically and therapeutically and may be used to prevent and/or treat an infection caused by ebolavirus, Marburgvirus, or arenavirus.

A method for the regulated removal of heterologous genetic material from disseminating viral vaccine vectors is provided.

The present disclosure provides a modified HSV-1 vector. The HSV-1 vector comprises an exogenous nucleotide sequence encoding an immunostimulatory factor and/or an anti-immune checkpoint antibody. The HSV-1 vector of the present disclosure can be used for treating cancers.

Provided herein are recombinant modified vaccinia Ankara (rMVA) viral vectors comprising heterologous nucleic acid inserts encoding one or more SARS-CoV2 proteins, peptides, or fragments thereof, operably linked to a promoter compatible with poxvirus expression systems that, upon expression, are capable of inducing protective immunity. The compositions can be used in a priming vaccination strategy or in a prime/boost vaccination strategy to provide immunity to SARS-CoV2 and variants thereof.

The present disclosure provides interleukin-36 (IL-36) cytokine (e.g., IL-36) expressing oncolytic viruses, and compositions comprising thereof. The present disclosure further provides methods of using said oncolytic viruses and compositions for treating cancer, and for improving a subject's responsiveness to an immunomodulatory agent.