The present invention includes antigenic fusion proteins, nucleic acids encoding the fusion proteins and methods of making and using the same, wherein the fusion protein comprises three or more different influenza A ectodomains of Matrix Protein 2 (M2e); one or more stem regions of an influenza A hemagglutinin 2 (HA2) protein; and optionally an anthrax antigen, wherein the fusion protein is immunogenic across strains.

Engineered Influenza polynucleotides, viruses, vaccines, and methods of making and using the same are provided. More specifically, the present inventors have developed replication competent engineered influenza viruses having, for example, a modified segment 4 and/or segment 6 that include at least one additional polynucleotide encoding a heterologous polypeptide.

The invention provides a composition useful to prepare influenza viruses, e.g., in the absence of helper virus, using vectors which include tandem transcription cassettes containing PolI and/or PolII promoters.

An Embodiment relates to a method comprising: co-expressing a viral vector of a virus of interest and a CD34 expression vector into a human cell line to produce virus particles such that CD34 incorporates into the virus particles; isolating the virus particles from the human cell line; blocking a viral infection; and wherein the method is configured for inhibiting the viral infection of the virus of interest.

RNA virus vectors comprising a gene encoding the DNA-dependent activator of interferon-regulatory factors (DAI) protein, and optionally further comprising a gene encoding the receptor-interacting serine/threonine-protein kinase 3 (RIPK3) may be used therapeutically to induce cell death, as well as an inflammatory immune response, against tumors and virally-infected cells.

A system and method that identifies and causes cancerous cells to self-destruct by using an engineered virus to vector and distinguish cancerous cells from normal cells through metabolic and other biometric signatures inherent in cancerous cells, identifies, binds and inserts itself into the cancer cell thereby causing the cell to identify and highlight itself as a target for natural intracellular and systemic cell-eradication pathways. Upon confirmatory binding, these engineered vectors, that specifically identify and target only cancer cells through binding to and then being absorbed into the cancer cells, fix the body's natural defenses that cancer cells evaded as part of cancer's progression to activate multiple paths for precisely targeted destruction of the hyperproliferating cells. In the development stages, the cancer cell must intensify its metabolism to support the prolific growth and at the same time the transforming cell must debilitate the intracellular and systemic checks against uncontrolled cell growth that the body has developed to maintain homeostasis. The vector of this invention is engineered to identify and bind cells expressing the intensified metabolic signatures required for cancer's growth, and then by inserting into the cell, to trigger natural intracellular defenses that, in responding to the vector, also prevent continuing metabolism of the cancer cell. The vector initiates dormant metabolic pathways that will, when activated, support eradication of the targeted cell through its natural apoptosis. Several of the compounds induced in response to the vector entry into the target cell also unleash a systemic effect by migrating to the cell membrane where: a) they serve as tags or markers of the infected cell; and b) by releasing cytokines, guide powerful killing cells from the immune system to the tagged cell. These natural processes provide additional backup measures to complete the destruction and removal of the targeted cancer cell.

The present invention provides chimeric negative-stand RNA viruses that allow a subject, e.g., an avian, to be immunized against two infectious agents by using a single chimeric virus of the invention. In particular, the present invention provides chimeric influenza viruses engineered to express and incorporate into their virions a fusion protein comprising an ectodomain of a protein of an infectious agent and the transmembrane and cytoplasmic domain of an influenza virus protein. Such chimeric viruses induce an immune response against influenza virus and the infectious agent. The present invention also provides chimeric Newcastle Disease viruses (NDV) engineered to express and incorporate into their virions a fusion protein comprising the ectodomain of a protein of an infectious agent and the transmembrane and cytoplasmic domain of an NDV protein. Such chimeric viruses induce an immune response against NDV and the infectious agent.

The invention provides a composition useful to prepare high titer influenza viruses, e.g., in the absence of helper virus, which includes internal genes from an influenza virus vaccine strain or isolate, e.g., one that is safe in humans, for instance, one that does not result in significant disease, that confer enhanced growth in cells in culture, such as MDCK cells, or in eggs.

The present invention relates to methods and compositions for enhancing expression from RNA expression vectores. The invention is based upon the observation that reducing the frequency of the dinucleotide CpG and UpA has a significant effect on expression from such vectores. Aspects of the invention include, amongst others, synthetic RNA vectores, virions, cells, methods of producing vaccines and methods of treatment or immunisation.

The invention provides a composition useful to prepare high titer influenza viruses, e.g., in the absence of helper virus, which includes internal genes from an influenza virus vaccine strain or isolate, e.g., one that is safe in humans, for instance, one that does not result in significant disease, that confer enhanced growth in cells in culture, such as MDCK cells, or in eggs.