Immunogenic constructs and vaccines are provided along with methods of use and manufacture thereof.

There are provided herein, inter alia, complexes, compositions and methods for the delivery of nucleic acid into a cell in vivo. The complexes, compositions and methods may facilitate complexation, protection, delivery and release of oligonucleotides and polyanionic cargos into target cells, tissues, and organs both in vitro and in vivo.

A composition is provided comprising an oligonucleotide aptamer conjugated to an antigen, wherein the aptamer is directed against a cell-surface target of an antigen-presenting cell. Also provided are methods of delivering an antigen to a dendritic cell and of eliciting an immune response in a subject.

The present invention is directed towards an artificial RNA nanostructure comprising multiple external strands of RNA, each external strand comprising about 40-50 nucleotides; one internal strand of RNA comprising more than about 50 nucleotides; the internal strands and external strands assembled to form a triangle nanostructure, a square nanostructure, or a polygon nanostructure and a pRNA three-way junction (3WJ) motif at each vertex of the nanostructure. Such nanostructure can be provided in a composition together with an adjuvant for use in inducing the production of high affinity neutralizing antibodies or inhibitory antibodies, inducing the production of cytokines, inducing an immune response in a subject, or a combination thereof.

The present invention provides nanostructures that are particularly well suited for delivery of bioactive agents to organs, tissues, and cells of interest in vivo, and for diagnostic purposes. In exemplary embodiments, the nanostructures are complexes of DNA strands having fully defined nucleotide sequences that hybridize to each other in such a way as to provide a pre-designed three dimensional structure with binding sites for targeting molecules and bioactive agents. The nanostructures are of a pre-designed finite length and have a pre-defined three dimensional structure.

This peptide/-1,3-glucan complex includes -1,3-glucan and a peptide/polynucleotide conjugate in which an antigenic peptide is bonded covalently to a polynucleotide or a derivative thereof. The polynucleotide or derivative thereof of the peptide/polynucleotide conjugate bonds via a hydrogen bond with -1,3-glucan, forming a complex having a triple helix structure including a single molecular chain of the polynucleotide or derivative thereof and two molecular chains of the -1,3-glucan. Alternatively, the side chain of the -1,3-glucan and the antigenic peptide are bonded covalently formed by either a cycloaddition reaction between an alkyne and an azide derivative, or a reaction between a maleimide group or a vinyl sulfone group and a thiol group.

Described herein are compositions composed of peptide nucleic acid strands. In some aspects the peptide nucleic acid strands are complementary to at least a portion of another peptide nucleic acid strand that may have one or more gamma substituents, where the ratio of PNA strands is least 1:1. Certain gamma substituents are capable of effecting attachment of a PNA strand to a cell. The disclosure also concerns construction of nanostructure platforms and vaccines and use of the inventive compositions in inhibiting disease states in mammals.

The disclosure is generally related to cross-linked tumor lysate spherical nucleic acids (CLSNAs), nanostructures comprising a core to which a shell of oligonucleotides is attached. Methods of making and using the CLSNAs are also provided herein. In some aspects, the disclosure provides a cross-linked tumor lysate spherical nucleic acid (CLSNA) comprising: (a) a core comprising a plurality of cross-linked tumor cell antigens; and (b) a shell of oligonucleotides attached to the external surface of the core, the shell of oligonucleotides comprising one or more immunostimulatory oligonucleotides.

Compositions containing a nucleic acid nanostructure having a desired geometric shape and an antigen and/or immunostimulatory agent(s) bound to its surface are provided. The nanostructure design allows for control of the relative position and/or stoichiometry of the immunostimulatory agent(s) bound to its surface. The antigen and/or immunostimulatory agent(s) displayed on the nanostructure surface are arranged with the preferred number, spacing, and 3D organization to elicit a robust immune response. The displayed antigen can be eOD-GT8. The immunostimulatory agent can be, e.g., T cell epitope such as a pan HLA DR-binding epitope (PADRE) and/or a lectin such as MBL or C3, or ligand thereof such as a glycan including mannose. Also provided are antigen-T cell epitope fusions such as eOD-PADRE and nanostructures presenting the same. The immunostimulatory compositions may thus be useful as immunogens, vaccines, adjuvants, and the like. Methods of inducing immune responses are also provided.

Provided are a virus peptide-protein subunit combination vaccine based on DNA nanotechnology, and a preparation method therefor and use thereof, which belong to the technical field of biological products. Provided is a virus peptide-protein subunit combination vaccine based on DNA nanotechnology, in which a tetrahedral framework nucleic acid formed by assembly of DNA strands is used as a vector, a protein antigen triggering virus-specific T cell activation is coupled to one edge of the tetrahedral framework nucleic acid, and B cell epitope peptides of a virus are coupled to four vertices of the tetrahedral framework nucleic acid.