Heptose-1-monophosphate-7-derivatives are modifiable immunomodulators that can be used to prepare clinically active conjugate compounds. Such conjugate compounds are useful in modulating an immune response in a subject.

Some aspects of this disclosure provide engineered exopolysaccharide-associated proteins, engineered bacteria expressing such proteins, and engineered biofilms comprising such proteins. Some aspects of this disclosure provide methods for engineering exopolysaccharide-associated proteins, and for the generation of engineered bacteria and biofilms expressing or comprising such proteins. Some aspects of this disclosure provide compositions and methods useful for the generation of vaccines and the vaccination of subjects, for delivering molecules of interest to a target site, for example, a surface, for purification of molecules of interest, for example, from bioreactors comprising engineered bacteria as provided herein, and for bioremediation applications, such as the cleanup of environmental pollutants.

Provided are methods for rapidly inactivating a pathogen, or for producing a vaccine composition containing an inactivated noninfectious pathogen having retained antigenicity and/or immunogenicity, comprising exposing the pathogen to a chemical inactivating agent (e.g., one or more chemical oxidizing, alkylating or crosslinking agents) in the presence of inorganic polyatomic oxyanions in an amount and for a time sufficient to render the pathogen noninfectious while enhancing retention of pathogen antigenicity and/or immunogenicity relative to that retained by contacting the pathogen with the chemical inactivating agent alone. The methods are broadly applicable to pathogens having RNA or DNA genomes (e.g., including viruses, bacteria, fungi, and parasites). Also provided are vaccine compositions (medicaments) containing a pathogen inactivated by exposure to a an inactivating agent in the presence of elevated concentrations of inorganic polyatomic oxyanions, and methods for eliciting an immune response in a subject by administering the vaccine compositions.

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.

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.

The present invention provides zwitterionic oligosaccharides, in particular fragments of the surface polysaccharides from Shigella sonnei and Shigella sonnei conjugates comprising them. The present invention also provides protected disaccharides, their process of preparation and their use in the synthesis of zwitterionic oligosaccharides, and conjugates thereof, the disaccharide repeating unit of Shigella sonnei being: (I)

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Adjuvants comprising chitosan cross-linked with an aldehyde or mannosylated chitosan are provided herein. Methods of making the adjuvants and methods of combining or linking the adjuvants with antigens are also provided. The adjuvant-antigen combinations can be used in vaccine formulations and the vaccine formulations can be used in methods to vaccinate animals against the source of the antigen or to enhance the immune response in a subject.

The invention is directed to immunogenic compositions and method of treatment comprising a peptide or nucleic acid that encodes the peptide that induces an immune response in a mammal that is protective against infection by one or more pathogens. The peptide sequence contains multiple epitopes, wherein at least one epitope is a composite epitope which is a combination of two or more conserved epitopes of the pathogen wherein the amino acid sequence of the composite is not an amino acid sequence of the pathogen. In addition, the invention is directed to vaccines comprising the peptide or nucleic acid that encodes the peptide for treating and preventing an infection in mammals such as animals and humans.

The present invention is directed to a bioconjugate vaccine, such as an O 1-bioconjugate vaccine, comprising: a protein carrier comprising a protein carrier containing at least one consensus sequence, DIE-X-N-Z-S/T, wherein X and Z may be any natural amino acid except proline; at least one antigenic polysaccharide from at least one pathogenic bacterium, linked to the protein carrier; and, optionally, an adjuvant. In another aspect, the present invention is directed to a method of producing an O 1-bioconjugate in a bioreactor comprising a number steps.

According to the invention, immunogenicity of an antigenic peptide is increased by administering a fusion protein, which comprises an antigenic peptide and an adjuvant protein, wherein the adjuvant protein comprises two or more proteins selected from the group consisting of a Shiga toxin 2e B subunit (Stx2eB), an Escherichia coli heat-labile toxin B subunit (LTB), and a cholera toxin B subunit (CTB). or a transformant transformed by a gene coding for the fusion protein.