The present invention provides methods for inducing regression of tumors in human subjects, the methods utilize a modified mesogenic strain of Newcastle disease virus (NDV) with modified F protein cleavage site, which is non-pathogenic to poultry (lentogenic), but exhibits oncolytic properties. The disclosed methods provide safe, effective and reliable means to induce regression of a tumor in an individual in need thereof. These methods overcome the drawbacks of using pathogenic strains of viruses for human therapy.

Provided are methods of identifying peptide epitopes of a major histocompatibility complex (MHC) molecule of an antigen, such as a tumor antigen, autoimmune antigen or pathogenic antigen. In some embodiments, the methods relate to using cytomegalovirus containing a nucleic acid molecule encoding the antigen to infect cells under conditions to generate particular peptide epitopes of the antigen. Also provided are methods of identifying peptide binding molecules that bind to a peptide epitope in the context of an MHC molecule. In some embodiments, the peptide binding molecule is a T cell receptor (TCR) or antibody, including antigen-binding fragments thereof and chimeric antigen receptors (CAR) thereof. Also provided are methods of genetically engineering cells containing such peptide binding molecules, and such genetically engineered cells, including compositions and uses thereof in adoptive cell therapy.

The present invention provides a recombinant turkey herpesvirus modified by the presence of the cDNA encoding the hemagglutinin protein of avian influenza virus under a promoter. A poultry vaccine comprising the recombinant turkey herpesvirus described in the present invention can induce serological responses that may be easily detected by the hemagglutination inhibition assay but not by commercially available diagnostic ELISA kits; thus enabling easy differentiation between vaccination and field infection.

Disclosed herein are CMV vectors that include a heterologous protein antigen, an active UL131 protein (or an ortholog thereof), an active UL128 protein (or ortholog thereof), but wherein the CMV vector lacks an active UL130 protein (or an ortholog thereof). Also disclosed herein are CMV vectors comprising: a heterologous protein antigen, an active UL131 protein (or an ortholog thereof), an active UL130 protein (or an ortholog thereof), but wherein the CMV vector lacks an active UL128 protein. Further disclosed are methods of using CMV vectors to generate an immune response characterized as having at least 10% of the CD8+ T cells directed against epitopes presented by MHC Class II.

A novel method for preventing or treating an infectious disease in a subject in need thereof. In particular the method includes the administration of a combination, pharmaceutical combination, medicament or kit-of-parts having a first part including a CD8 vaccine specific for at least one infectious disease-related antigen, a second part including an agent neutralizing circulating alpha interferon and/or an agent blocking interferon alpha signaling, and/or a third part including a type III interferon and/or an agent stimulating the production of type III interferon.

Human cytomegalovirus vectors comprising heterologous antigens are disclosed. The vectors derived from the TR strain, are ganciclovir-sensitive, include active US2, US3, US6, US7 and UL131A genes, and have a deleterious or inactivating mutation in the UL82 gene preventing the expression of pp71.

A novel method for gene therapy using intranasal administration of genetically modified viral vectors. Target genes for therapeutic administration to a human patient, for many purposes such as production of telomerase in a patient's body, are selected and transfected into a bacterial cell. Viral transduction is used to infect a human-administrable virus with the target genes in the bacterial cell. A solution containing a therapeutic amount of transfected viral agents is intranasally administered the solution into a human patient.

Disclosed herein are vector systems for expression of polypeptides in eukaryotic cells; and methods of obtaining high-level expression of polypeptides in a eukaryotic cell. Methods and compositions for obtaining stable, long-term expression of recombinant polypeptides are also provided.

Disclosed are CMV vectors that lack active UL128, UL130, UL146 and UL147 proteins that may also comprise one or more microRNA regulatory elements (MRE) that restrict expression of the CMV. Immunization with the disclosed CMV vectors allow selection of different CD8+ T cell responsesCD8+ T cells restricted by MHC-Ia, MHC-II, or by MHC-E.

The present invention provides methods for inducing regression of tumors in human subjects, the methods utilize a modified mesogenic strain of Newcastle disease virus (NDV) with modified F protein cleavage site, which is non-pathogenic to poultry (lentogenic), but exhibits oncolytic properties. The disclosed methods provide safe, effective and reliable means to induce regression of a tumor in an individual in need thereof. These methods overcome the drawbacks of using pathogenic strains of viruses for human therapy.