The present disclosure provides T-cell modulatory multimeric polypeptides that comprise an immunomodulatory polypeptide that exhibits reduced binding affinity to a cognate co-immunomodulatory polypeptide. A T-cell modulatory multimeric polypeptide is useful for modulating the activity of a T cell, and for modulating an immune response in an individual.

The present invention comprises compositions, methods, and devices for enhancing an endogenous immune response against a cancer. Devices and methods provide therapeutic immunity to subjects against cancer.

The present invention relates to a composition comprising an isolated, single stranded RNA molecule having a nucleotide sequence comprising 20 or more bases and a pattern of CpG dinucleotides defined by a strength of statistical bias greater than or equal to zero, and a pharmaceutically acceptable carrier suitable for injection. The present invention also relates to a kit comprising a cancer vaccine and the composition of the present invention as an adjuvant to the cancer vaccine. The present invention further relates to a method of treating a subject for a tumor and a method of stimulating an immune response.

Compositions containing a nucleic acid nanostructure having a desired geometric shape and antigens bound to its surface are provided. The nanostructures can be, for example, in the form of a 6-helix bundle or icosahedron. The nanostructure design allows for control of the relative position and/or stoichiometry of the antigen bound to its surface. The antigens 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 an HIV immunogen such as eOD-GT6, eOD-GT8, or variants thereof. The compositions may thus be useful as immunogens, vaccines, immunostimulators, adjuvants, and the like. Methods of inducing immune responses, inducing protective immunity, inducing the production of neutralizing antibodies or inhibitory antibodies, inducing tolerance, and treating cancer, infectious or autoimmune diseases are also provided.

A fusion protein is provided which is based on a self-assembling gene-regulatory NSP10 protein and a protein or peptide capable of being fused to NSP10 without interfering with the assembly or aggregation of the resulting fusion protein. The disclosure also relates to any nanoparticle formed thereby whether complete or not, and methods for the use of the NSP10 fusion protein are also disclosed, including use as vaccines for any indication in humans or animals, therapeutic methods involving the use of the fusion proteins such as using the protein to targeted an antibody or receptor, such as for treating or diagnosing cancer, biosensors using the fusion protein, or the use of the fusion proteins in cell sorting or any imaging application.

The disclosure describes compositions containing conjugates using novel linkers, bivalent polysaccharide conjugates, and methods of bivalent polysaccharide conjugation in the development of multivalent conjugate vaccines. Conjugation of capsular polysaccharides to carrier proteins is carried out using homo-bifunctional and/or hetero-bifunctional linkers of specific lengths. Incorporation of the linkers and their use in bifunctional linkers induces higher titers of functional antibodies with high avidity, eliciting higher immunologic memory, and reduced carrier protein effect. This provides immunochemically cross-reactive capsular polysaccharides wherein one or more cross-reactive capsular polysaccharides are conjugated sequentially or concurrently to carrier protein using bifunctional linkers bearing the same or different functional groups. Such a linker and the size of the capsular polysaccharides provides an effective multivalent conjugate vaccine with high antibody titers and a reduced carrier effect and results in reduction in the content of the capsular polysaccharide and protein per dose of vaccine which reduces reactogenicity.

The present invention relates to compositions and kits comprising a peptide that activate the immune response and methods of using the composition for immunotherapy and cancer treatments. The peptide comprises an active peptide sequence of VQATQSNQHTPR. In some embodiments, the peptide may be tetravalent. For example, the peptide has the structure [(VQATQSNQHTPRGGGS).sub.2K].sub.2KNH.sub.2. In some embodiments, the compositions and methods are directed to the treatment of cancer and/or infections.

Engineered exosomes for the delivery of bioactive cargo are provided. The exosomes incorporate a tetraspanin transmembrane anchoring scaffold onto the membrane of the exosome. The tetraspanin transmembrane anchoring scaffold has a C-terminal attachment site in the inner-vesicle space of the exosome, a N-terminal attachment site in the inner-vesicle space or the outer-vesicle space, and/or a loop attachment site in the outer-vesicle space. Peptides can be attached to the different attachments sites in any form or combination. Tetrapanins naturally anchor on the exosome membrane, are biocompatible, and allow for robust loading and delivery of bioactive cargos in mammalian system.

Multilayer films comprise polypeptide epitopes from Plasmodium falciparum, specifically a circumsporozoite CIS43 epitope and one or more of circumsporozoite T1, B or T* epitope. The multilayer films are capable of eliciting an immune response in a host upon administration to the host. The multilayer films can include at least one designed peptide that includes one or more polypeptide epitopes from a Plasmodium protozoan.

This disclosure provides nano-scale Artificial Antigen Presenting Cells (aAPC), which deliver stimulatory signals to lymphocytes, including cytotoxic lymphocytes, for use as a powerful tool for immunotherapy.