The present invention relates to an immunostimulatory composition comprising a) an adjuvant component, comprising or consisting of at least one (m)RNA, complexed with a cationic or polycationic compound, and b) at least one free mRNA, encoding at least one therapeutically active protein, antigen, allergen and/or antibody, wherein the immunostimulatory composition is capable to elicit or enhance an innate and optionally an adaptive immune response in a mammal. The inventive immunostimulatory composition may be a pharmaceutical composition or a vaccine. The invention furthermore relates to a method of preparation of the inventive immunostimulatory composition. The invention also relates to the use of the inventive immunostimulatory composition or its components (for the preparation of a pharmaceutical composition or a vaccine) for the treatment of various diseases. Finally, the invention relates to kits containing the inventive immunostimulatory composition, its components and/or the pharmaceutical composition or vaccine.

In one aspect, a method of treating cancer in a mammal is provided. The method comprises administering to the mammal an oncolytic vector that expresses a tumor antigen to which the mammal has a pre-existing immunity. In another aspect, a method of boosting immune response in a mammal having a pre-existing immunity to an antigen is provided comprising intravenous administration to the mammal of a B-cell infecting vector that expresses the antigen.

Compositions and methods are provided herein for improved dual immunization strategies that induce in a subject a robust immune response. The methods described are therefore useful for treating and/or preventing (i.e., reducing the likelihood or risk of occurrence) different diseases, disorders, and conditions such as cancers and infectious diseases for which induction of a humoral immune response and/or cellular immune response is desired and beneficial.

As described below, the present invention features methods for enhancing the efficacy of a tumor antigen in inducing an anti-cancer immune response in a subject by administering an OX40 agonist and an Indoleamine 2,3-dioxygenase (IDO) inhibitor with the tumor antigen.

The present invention relates to a recombinant bacterium expressing an antigen that is translocated to the cytosol of a host organism, and uses thereof. To this end, the present invention provides a recombinant bacterium comprising a nucleic acid encoding an antigen that is translocated to the cytosol of a host cell utilizing Type Ill secretion system. The recombinant bacterium is generally chosen from intracellular pathogens that reside in the phagosome and fail to induce rapid T cell activation. The translocated antigen may be a viral antigen, a bacterial antigen, or a tumour antigen. Methods of imparting immunity using the recombinant bacterium are also provided.

Compositions are provided comprising a replication-competent herpesvirus vector system and/or a herpesvirus vector particle comprising a heterologous recombinant transgene of interest encoding an antigen of interest (e.g., a tumor-associated antigen, a microbial antigen, etc.), wherein the recombinant transgene has been modified to comprise a codon usage signature of a herpesvirus late gene operably linked to an active promoter. Such compositions find use in a variety of methods including, for example, methods of generating an immune response against an antigen of interest in a subject in need thereof, as well as methods for treating or preventing cancer or a microbial infection.

The invention provides CD27 agonists comprising a first component that is an anti-CD27 antibody, or antigen-binding fragment thereof, linked to a second component comprising one or more cross-linking moieties. At least one of the cross-linking moieties does not bind to an Fc receptor and the CD27 agonist stimulates T cell activity without the need for Fc receptor interaction. The cross-linking molecule(s) can be, for example, an anti-CD27, antibody, or antigen-binding fragment thereof, that can be the same or different than the first component. Alternatively, the cross-linking molecule(s) can be a CD27 ligand or a molecule (e.g., antibody) that binds a molecule on a cell such as a T cell, a tumor cell or a stromal cell. Pharmaceutical compositions comprising the CD27 agonists, and methods of using the CD27 agonists, are also provided.

Compositions comprising donor cells, acceptor cells, and methods involving the same are described herein. In some embodiments, the donor cell is deficient in at least one endogenous function, for instance cytotoxic activity. In some embodiments, the donor cell comprises a T cell receptor (TCR) and a cargo, and the acceptor cell comprises an MHC. In some embodiments, the TCR facilitates transfer of the cargo to the acceptor cell. In some embodiments, the donor cell comprises a chimeric antigen receptor (CAR) and a cargo, and the acceptor cell comprises an antigen bound by the CAR. In some embodiments, the CAR facilitates transfer of the cargo to the acceptor cell.

Materials and methods for identifying and using MHC molecule variants for activating self-reactive T cells in a peptide-specific manner, and their use to focus autoimmune cellular responses against diseases such as cancers and persisting viral infections, are described.

The invention provides liposomes containing nonglycosidic ceramides within their bilayers, and compositions thereof. These liposomes activate murine iNKT cells and induce dendritic cell (DC) maturation, both in vitro and in vivo at an efficacy that is comparable to their corresponding soluble nonglycosidic ceramides. Also provided are methods for treating diseases using the liposomes and compositions of the invention.