Provided are immunogenic compositions comprising a secreted fusion protein, wherein the secreted fusion protein comprises a soluble influenza or rabies viral antigen joined by in-frame fusion to a C-terminal portion of a collagen which is capable of self-trimerization to form a disulfide bond-linked trimeric fusion protein. Also provided are uses of the immunogenic compositions for generating an immune response against influenza or rabies infection and in a vaccine composition. Also provided are methods for producing the recombinant peptides and proteins, prophylactic, therapeutic, and/or diagnostic methods, and related kits.

The present disclosure is directed towards chimeric glycoproteins wherein the clip region, a core region, a flap region, and a transmembrane and cytoplasmic domain are defined by starting from the amino terminus of the protein, these domains are comprised of the following amino acid residue ranges: clip, 1 through 40 to 60; core, 40 to 60 through 249 to 281; flap, 249 to 281 through 419 to 459; the transmembrane domain is comprised of amino acids 460 through 480, and the remaining amino acids 481 through 525 comprise the cytoplasmic domain; and wherein the clip, core, flap, transmembrane, and cytoplasmic domain comprise a chimeric combination of at least two lyssavirus, wherein the chimeric glycoprotein is advantageously inserted into a rabies-based vaccine vector.

The present disclosure is directed towards chimeric glycoproteins wherein the clip region, a core region, a flap region, and a transmembrane and cytoplasmic domain are defined by starting from the amino terminus of the protein, these domains are comprised of the following amino acid residue ranges: clip, 1 through 40 to 60; core, 40 to 60 through 249 to 281; flap, 249 to 281 through 419 to 459; the transmembrane domain is comprised of amino acids 460 through 480, and the remaining amino acids 481 through 525 comprise the cytoplasmic domain; and wherein the clip, core, flap, transmembrane, and cytoplasmic domain comprise a chimeric combination of at least two lyssavirus, wherein the chimeric glycoprotein is advantageously inserted into a rabies-based vaccine vector.

The invention provides adenoviral vectors comprising transgenes encoding Lyssaviral antigens. The vectors can be used to produce vaccines for the prophylaxis, amelioration and treatment of diseases caused by Lyssaviral diseases, e.g., rabies.

Provided herein are pseudotyped recombinant lyssavirus particles and methods for their use in delivering a transgene into a target cell. Also provided are packaging systems and methods of using the packaging systems to produce pseudotyped recombinant lyssavirus particles.

The disclosure provides for methods and compositions for treating a premature aging disorder or neurodegenerative disorder, particularly neurodegenerative disorders associated with amyloid deposition and neuronal death, such as Alzheimer's disease. Accordingly, aspects of the disclosure relate to a method for treating a premature aging disorder in a subject in need thereof, comprising administering a TERT activating therapy to the subject. Further aspects relate to a method for treating a neurodegenerative disorder in a subject comprising administering a TERT activating therapy to the subject.

The present invention relates to a composition comprising (a) a recombinant rhabdovirus vector capable of forming a virus particle and expressing an immunogen of a betacoronavirus, wherein the immunogen comprises at the C-terminus a heterologous transmembrane anchor for the incorporation of the immunogen into (i) the cell membrane of infected cells, and (ii) the envelope of the virus particle, and/or (b) a glycoprotein (G) protein gene deleted and in trans G protein complemented recombinant rhabdovirus vector capable of forming a virus-like particle (VLP) and expressing an immunogen of a betacoronavirus, wherein the immunogen comprises at the C-terminus a heterologous transmembrane anchor for the incorporation of the immunogen into (i) the cell membrane of infected cells, and (ii) the VLP.

Provided is a method of enhancing an antigen-induced long-lasting immune response in a host comprising administering to a host an effective amount of: (a) a nonpathogenic recombinant rabies virus comprising at least three copies of a mutated G gene, wherein said mutated G gene encodes a rabies virus glycoprotein wherein the glycoprotein amino acid 194 is serine and the glycoprotein amino acid 333 is glutamic acid, wherein said recombinant rabies virus does not express a foreign protein antigen; and (b) a Coronavirus antigen that is not expressed by the rabies virus. Also provided are related compositions, kits and vaccines.

Provided herein are delivery particle systems (XDP) useful for the delivery of payloads of any type. In some embodiments, a XDP particle system with tropism for target cells of interest is used to deliver CRISPR/Cas polypeptides (e.g., CasX proteins) and guide nucleic acids (gNA), for the modification of nucleic acids in target cells. Also provided are methods of making and using such XDP to modify the nucleic acids in such cells.

The invention is in the domain of delivery of molecules to brain cells across the blood-brain barrier. The invention relates to a novel polypeptide-based carrier that allows the efficient delivery of an effector peptide, to neuron cells across the blood-brain barrier, and to methods for the production and testing of such carrier, including a model for testing the capacity of such molecule to cross the blood-brain barrier and/or the toxicity of molecules on the blood brain barrier and/or the capacity of molecules that have crossed to target human brain cells (e/g. neurons, astrocytes and microglial cells).