The present disclosure is related to immunomodulatory bacterial minicells and methods of using the minicells.

A vaccine platform using a Yersinia pestis mutant synthesizing an adjuvant form lipid A (monophosphoryl lipid A, MPLA) for the increased biogenesis of bacterial outer membrane vesicles (OMVs). To enhance the immunogenicity of the OMVs, an Asd-based balanced-lethal host-vector system was constructed to oversynthesize the LcrV antigen of Y. pestis, raise the amounts of LcrV enclosed in OMVs by Type II secretion system, and eliminate harmful factors like plasminogen activator (Pla) and murine toxin from the OMVs. Vaccination with OMVs containing MPLA and increased amounts of LcrV with diminished toxicity afforded complete protection in mice against subcutaneous challenge and intranasal challenge and was significantly superior to that resulting from vaccination with LcrV/alhydrogel. Additionally, the Yersinia OMV can be used as a platform to deliver the heterologous antigens of Bacillus anthraces. Vaccination with multiantigenic self-adjuvanting bionanoparticles from Pseudomonas was also successfully tested in connection with Pseudomonas aeruginosa.

Certain embodiments are directed to an attenuated bacterial platform for autotransporter-mediated display of antigens. In certain aspects the display is surface display or periplasmic display. In other aspects the antigen is a microbial antigen. The microbial antigen can be a bacterial or viral antigen. The antigen can be antigen derived from a biothreat.

This invention describes method for inactivation of microorganisms in thermostable dry formulations at ambient temperatures (AT) using UV light irradiation. According to this method microorganisms are inactivated at ambient temperatures (AT) in dry formulations where the amount of free radicals formed is relatively small and damage of nucleic acids is the main cause for the microorganism's death. The method will allow production of thermostable inactivated vaccines from wild type and live attenuated microorganisms, thermostable inactivated microbiome products, and thermostable sterilized none-live blood components, therapeutic proteins, antibodies and other fragile biopharmaceuticals.

Described herein are methods and compositions relating to vaccinating, immunizing, or inducing an immune response in an immune distinct subject. In some embodiments, the methods and compositions relate to a first cytokine mRNA construct comprising a first open reading frame (ORF), wherein the first ORF encodes a proinflammatory cytokine; and optionally, one or more of: a first antigen mRNA construct comprising a second open reading frame (ORF), wherein the second ORF encodes an antigen; and an antigen polypeptide, antigen molecule, or killed or attenuated pathogenic agent. The methods and compositions described herein provide adjuvantation that overcomes the resistance of immune distinct patients to vaccination, permitting more effective vaccination, as well as the ability to reduce dosages, reduce the need for boosters, and permit antigen stacking to immunize more comprehensively.

The present disclosure relates to immunogenic compositions comprising at least one Yersinia pestis (Y. pestis) antigen, an aluminum salt adjuvant, and an oligonucleotide comprising an unmethylated cytidine-phospho-guanosine (CpG) motif. The immunogenic compositions are suitable for stimulating an immune response against Y. pestis in a subject in need thereof. The present disclosure also relates to kits and methods using the immunogenic compositions, or two separate compositions which together comprise the antigen, the aluminum salt adjuvant, and the oligonucleotide.

The present disclosure relates generally to chimeric polypeptides that comprise a microbial polypeptide (preferably (a) a virion surfaced exposed portion of an enveloped viral fusion protein or (b) a bacterial outer membrane polypeptide) and a heterologous structure-stabilizing moiety, and to complexes comprising those chimeric polypeptides. The present disclosure also relates to the use of these chimeric polypeptides and complexes thereof in compositions and methods for eliciting an immune response to a microbial polypeptide (preferably a fusion protein of an enveloped virus or a bacterial outer membrane polypeptide), or to respective complexes thereof and/or for treating or preventing related microbial infection (preferably an enveloped virus infection or a bacterial infection). Moreover, the disclosure further relates to compositions and methods for producing an antigen-binding molecule that specifically binds to such a microbial polypeptide or a complex thereof (preferably to an enveloped viral fusion protein or a complex thereof, or to a bacterial outer membrane polypeptide or a complex thereof).

Compositions and methods of using the same wherein the compositions include particles comprising one or more materials soluble in a solvent that is suitable for spray drying and one or more antigenic and/or non-antigenic payloads entrapped within the particles, wherein the composition is stable at room temperature for at least six months.

The present disclosure relates to immunogenic compositions comprising at least one Yersinia pestis (Y. pestis) antigen, an aluminum salt adjuvant, and an oligonucleotide comprising an unmethylated cytidine-phospho-guanosine (CpG) motif. The immunogenic compositions are suitable for stimulating an immune response against Y. pestis in a subject in need thereof. The present disclosure also relates to kits and methods using the immunogenic compositions, or two separate compositions which together comprise the antigen, the aluminum salt adjuvant, and the oligonucleotide.

Embodiments of the present disclosure provide novel compositions and methods for making and using thermostable polynucleotide-containing formulations. In certain embodiments, compositions and methods are disclosed for creating thermostable polynucleotides and/or thermostable polynucleotides encoding at least one therapeutic agent for use in therapies for the treatment of health conditions in a subject. In some embodiments, compositions and methods are disclosed for creating thermostable polynucleotides for use in therapeutics, vaccines, and targeted gene therapies. In other embodiments, compositions and methods are disclosed for creating thermostable polynucleotides capable of being coated or encased for prolonged storage and/or timed-delivery.