The present invention relates to the use of NS1/2 region of murine norovirus MNV or a corresponding region from a member of the Caliciviridae family or a protein encoded by any one of those regions, for treating dysbiosis, immune system dysregulation and various disorders, as well as for enhancing mucosal integrity and stimulating IFN-induced genes.

In one aspect, provided herein is a heterologous boost method for inducing an immune response to at least one neoantigen, the method comprising administering to a subject a first boost and subsequently administering to the subject a second boost, wherein the first boost comprises a first oncolytic virus comprising a genome that expresses, in the subject, a first peptide, or the first boost comprises a first oncolytic virus and a second peptide, wherein the second boost comprises a second oncolytic virus comprising a genome that expresses, in the subject, a third peptide, or the second boost comprises a second oncolytic virus and a fourth peptide, wherein the first peptide, the second peptide, the third peptide, and the fourth peptide are each capable of inducing an immune response to at least one neoantigen, and wherein the second oncolytic virus is immunologically distinct from the first oncolytic virus. The subject may have pre-existing immunity to the at least one neoantigen. The subject may have been administered a priming composition before receiving the first boost, wherein the priming composition is capable of inducing an immune response to the at least one neoantigen.

The present disclosure relates to a sequential boost oncolytic viral immunotherapy and compositions for use in the same. More particularly, the disclosure relates to oncolytic viruses that significantly increase antigen-specific T cell-mediated immune responses when combined in a sequential heterologous boost treatment regimen.

The present invention relates to the use of NS1/2 region of murine norovirus MNV or a corresponding region from a member of the Caliciviridae family or a protein encoded by any one of those regions, for treating dysbiosis, immune system dysregulation and various disorders, as well as for enhancing mucosal integrity and stimulating IFN-induced genes.