A composition comprising Shigella-Tetravalent (4-valent Shigella) bioconjugates. That encompasses the Shigella O-polysaccharide antigens of serotypes Shigella flexneri 2a, 3a, 6 and Shigella sonnei covalently linked to the protein carrier.

Provided are surprisingly effective methods for inactivating pathogens, and for producing highly immunogenic vaccine compositions containing an inactivated pathogen rendered noninfectious by exposure to a Fenton reagent, or by exposure to a Fenton reagent or a component thereof in combination with a methisazone reagent selected from the group consisting of methisazone, methisazone analogs, functional group(s)/substructure(s) of methisazone, and combinations thereof. The methods efficiently inactivate pathogens, while substantially retaining pathogen antigenicity and/or immunogenicity, and are suitable for inactivating pathogens, or for the preparation of vaccines for a wide variety of pathogens with genomes comprising RNA or DNA, including viruses and bacteria. Also provided are highly immunogenic inactivated vaccine compositions prepared by using any of the disclosed methods, and methods for eliciting an immune response in a subject by administering such vaccine compositions.

A Shigella vaccine preparation comprising 10E8-10E12 CFU of a live, genetically attenuated Shigella flexneri strain that comprises a chromosomal deletion of setBA and which is non-invasive as determined by the Sereny test and an in vitro invasion assay using HeLa cells, wherein the strain comprises an endogenous invasion plasmid that is genetically engineered to incorporate a heterologous expression construct expressing a pathogen-specific antigen.

The present disclosure relates to Salmonella Gallinarum mutant strains and uses thereof. A vaccine composition according to an aspect has no risk of reverting to pathogenicity, has no residual pathogenicity due to detoxification of an endotoxin, and does not cause lesions and bacterial re-isolation, thereby exhibiting significantly improved safety compared to the existing fowl typhoid vaccines. In addition, since the vaccine composition induces a high-level immune response even when administered to young chicks, it may be used regardless of age, and as the vaccine strain may be used as a live vaccine having an excellent protective capability by itself, the vaccine composition may be useful for preventing and alleviating fowl typhoid.

Disclosed is the attenuated Salmonella typhi vaccine Ty21a utilized as a vector for Shigella and/or enterotoxogenic E. coli genes stably integrated in the Ty21a chromosome. These genes include a heterologous Shigella sonnei O-antigen biosynthetic gene region that comprises the wzz gene and expresses Shigella sonnei form 1 O-antigen, as well as a heterologous acid resistance biosynthetic gene system comprising a YbaS gene, which enables increased stability of the Ty21a vector at pH 2.5 relative to Ty21a without the integrated acid resistance biosynthetic gene system.

The present invention relates to toxoid preparations comprising a non-disrupted and/or a non-denatured toxin associated with a particulate vector that minimizes or precludes said toxin from inflicting damage at an action site of said toxin. The present invention also relates to immunogenic compositions or vaccines comprising the toxoid preparations, and the methods of using the toxoid preparations, immunogenic compositions or vaccines.

The present invention relates to an attenuated strain of Salmonella comprising at least one copy of a DNA molecule comprising an expression cassette encoding PD-L1. In particular, the present invention relates to said attenuated strain of Salmonella for use in the treatment of cancer.

Provided are delivery immunostimulatory bacteria that have enhanced colonization of tumors, the tumor microenvironment and/or tumor-resident immune cells, and enhanced anti-tumor activity. The immunostimulatory bacteria are modified by deletion of genes encoding the flagella, or by modification of the genes so that functional flagella are not produced, and/or are modified by deletion of pagP or modification of pagP to produce inactive PagP product. As a result, the immunostimulatory bacteria are flagellin.sup.− and/or pagP.sup.−. The immunostimulatory bacteria optionally have additional genomic modifications so that the bacteria are adenosine or purine auxotrophs. The bacteria optionally are one or more of asd.sup.−, purI.sup.−, and msbB.sup.−. The immunostimulatory bacteria, such as Salmonella species, are modified to encode immunostimulatory proteins that confer anti-tumor activity in the tumor microenvironment, and/or are modified so that the bacteria preferentially infect immune cells in the tumor microenvironment, or tumor-resident immune cells, and/or are modified to induce less cell death in immune cells than in other cells. Also provided are methods of inhibiting the growth or reducing the volume of a solid tumor by administering the immunostimulatory bacteria.

The present invention relates to modified bacterial polypeptides having immunomodulatory and immunostimulatory activity. Most specifically, the present invention relates to modified bacterial polypeptides having an amino acid sequence selected from SEQ ID NO. 1, SEQ ID NO. 2, SEQ ID NO. 3, SEQ ID NO. 4 and SEQ ID NO. 5. The modified polypeptides are the adjuvant components of a pharmaceutical composition for eliciting an immune response against an specific antigen present in the pharmaceutical composition. In a preferred embodiment, the invention provides a pharmaceutical composition for a vaccine which comprises an adjuvant component which is any one of the modified polypeptides, one or more antigens, together with a pharmaceutically acceptable excipient.

Provided are surprisingly effective methods for inactivating pathogens, and for producing highly immunogenic vaccine compositions containing an inactivated pathogen rendered noninfectious by exposure to a Fenton reagent, or by exposure to a Fenton reagent or a component thereof in combination with a methisazone reagent selected from the group consisting of methisazone, methisazone analogs, functional group(s)/substructure(s) of methisazone, and combinations thereof. The methods efficiently inactivate pathogens, while substantially retaining pathogen antigenicity and/or immunogenicity, and are suitable for inactivating pathogens, or for the preparation of vaccines for a wide variety of pathogens with genomes comprising RNA or DNA, including viruses and bacteria. Also provided are highly immunogenic inactivated vaccine compositions prepared by using any of the disclosed methods, and methods for eliciting an immune response in a subject by administering such vaccine compositions.