The present invention relates to a vaccine suitable for immunisation against influenza, plague or Y. pestis infection said vaccine comprising outer membrane vesicles (OMVs) and the plague vaccine including the V and/or F1 antigens of Y. pestis.

Bivalent immunogenic compositions against anthrax and plague are disclosed herein. One bivalent immunogenic composition comprises a triple fusion protein containing three antigens, F1 and V from Yersinia pestis and PA antigen from Bacillus anthracia fused in-frame and retaining structural and functional integrity of all three antigens. Another bivalent immunogenic composition comprises bacteriophage nanoparticles arrayed with these three antigens on the capsid surface of the bacteriophage nanoparticles. These bivalent immunogenic compositions are able to elicit robust immune response in a subject administered said the bivalent immunogenic compositions and provide protection to the subject against sequential or simultaneous challenge with both anthrax and plague pathogens.

Provided herein are methods for using compositions that include a fusion protein having a YscF protein domain, a mature F1 protein domain, and a LcrV protein domain. In one embodiment the composition is used to confer immunity to plague, such as pneumonic plague, caused by Yersinia pestis. In one embodiment, the composition is administered to a mucosal surface, such as by an intranasal route. In one embodiment, the administration to a mucosal surface includes a vector that has a polynucleotide encoding a fusion protein, where the fusion protein includes a YscF protein domain, a mature F1 protein domain, and a LcrV protein domain. The administration is followed by a second administration by a different route, such as an intramuscular route. The second administration includes a fusion protein having the same three domains, and in one embodiment the fusion protein is the same one administered to a mucosal surface.

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

Bacterial live vector vaccines represent a vaccine development strategy that offers exceptional flexibility. In the present invention, genes encoding protective antigens of unrelated bacterial, viral, parasitic, or fungal pathogens are expressed in an attenuated bacterial vaccine strain that delivers these foreign antigens to the immune system, thereby eliciting relevant immune responses. Rather than expressing these antigens using only low copy expression plasmids, expression of foreign proteins is accomplished using both low copy expression plasmids in conjunction with chromosomal integrations within the same live vector. This strategy compensates for the inherent disadvantage of loss of gene dosage (versus exclusive plasmid-based expression) by integrating antigen expression cassettes into multiple chromosomal sites already inactivated in an attenuated vector.

Disclosed herein are compositions comprising immunomodulatory and oncolytic eubacterial minicells, and the use of the composition in immunomodulatory therapies for cancer. In some embodiments, the minicells are used in combination of immune checkpoint inhibitors in treating cancer.

A vaccine composition is disclosed that contains a vaccine antigen and a neutrophil inhibitor in amounts effective to promote an IgA response to the antigen in a subject. Also disclosed is a method for enhancing immune response to a vaccine antigen in a subject that involves co-administering to the subject the vaccine antigen and an adjuvant composition comprising a neutrophil inhibitor in an amount effective to promote an IgA response to the vaccine antigen in the subject.

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.

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

The disclosure relates to a composition comprising one, two or more immunogenic bacterial polypeptides and multivalent and monovalent vaccine compositions comprising the immunogenic bacterial polypeptides.