Glycoconjugate vaccines comprising basic units of a molecular construct expressing built-in multiple epitopes for the formulation of a broad-spectrum vaccine against infections due to enteropathogenic bacteria
Inventors
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Assignees
Member
BiosYnth s.r.l.BiosYnth s.r.l. is a biotechnology firm specializing in the research, development, and innovation of bacterial and viral vaccine platforms. With over 40 years of expertise, the company focuses on glycoconjugate, nanostructured vector, and synthetic peptide technologies to address invasive infectious diseases and antibiotic resistance. Operations comply with GLP and GMP standards and are supported by a robust patent portfolio and international collaborations.
BiosYnth s.r.l. is a biotechnology firm specializing in the research, development, and innovation of bacterial and viral vaccine platforms. With over 40 years of expertise, the company focuses on glycoconjugate, nanostructured vector, and synthetic peptide technologies to address invasive infectious diseases and antibiotic resistance. Operations comply with GLP and GMP standards and are supported by a robust patent portfolio and international collaborations.
Publication Number
US-11576959-B2
Publication Date
2023-02-14
Expiration Date
Abstract
The present invention refers to new glycoconjugate antigens expressing built-in multiple epitopes and to polyvalent glycoconjugate vaccines intended for the protection of mammalians, and particularly for the protection of the human population from enteropathogenic bacteria, such as the Gram-positive anaerobic bacterium Clostridium difficile and the Gram-negative bacteria Salmonella typhi, Escherichia Coli, Vibrio Cholerae, Shigella flexneri, Salmonella typhimurium, Salmonella enteritidis, Salmonella paratyphi A, Shigella sonnei, Shigella dysenteriae, Salmonella cholerasuis, Klebsiella, Enterobacter, Pseudomonas aeruginosa and/or from viral gastrointestinal infections due to human noroviruses.
Core Innovation
The invention relates to glycoconjugate vaccine antigens and vaccines comprising an antigenic multivalent molecular construct built from a helper-T dependent carrier detoxified protein selected between Enterotoxoid A and Cytotoxoid B from Clostridium difficile. In the multivalent construct, the detoxified carrier is covalently bound to a minimum of three carbohydrate structures from enteropathogenic bacteria, selected between bacterial polysaccharides or detoxified lipopolysaccharides, and each carbohydrate structure comprises at least one repeating basic epitope.
The repeating basic epitopes consist of a minimum of five to twelve monosaccharide residues, and the carbohydrate structures are of different serological specificity. The LPS component is detoxified to form Endotoxoid to avoid Lipid A-mediated toxicity, and the resulting detoxified lipopolysaccharide or Endotoxoid is included as a covalently bound carbohydrate structure.
The disclosed vaccines target enteropathogenic bacteria in a broad-spectrum manner, including Clostridium difficile and multiple enteric bacteria. Example constructs and characterization are described, including NMR, GPC, inhibition-ELISA and MIC50-based serological quantification, along with murine immunogenicity using IgG titers against carried polysaccharides or LPS or endotoxic components and anti-toxoid neutralization.
Claims Coverage
The partial content provides one independent method claim. It combines a helper-T dependent carrier detoxified protein, multivalency defined by at least three carbohydrate structures, defined repeating carbohydrate epitopes, and covalent binding with molar constraints, with optional pharmaceutically acceptable adjuvant or excipient.
Protection via antigenic multivalent glycoconjugate vaccine construct
A method for the protection of a subject from systemic and enteric infections due to at least one of the enteropathogenic bacteria selected among Clostridium difficile, Salmonella typhi, Escherichia coli, Vibrio cholerae, Salmonella enteritidis, Shigella flexneri, Shigella sonnei, Salmonella paratyphi A, Salmonella dysenteriae, Salmonella cholerasuis, Klebsiella, Enterobacter or a combination thereof, comprising administering an effective amount of a vaccine comprising an antigenic multivalent molecular construct.
Helper-T dependent carrier detoxified proteins covalently bound to multiple carbohydrates
The antigenic multivalent molecular construct consists of basic units comprising the helper-T dependent carrier detoxified proteins selected between Enterotoxoid A and Cytotoxoid B from Clostridium difficile covalently bound to a minimum of three carbohydrate structures from enteropathogenic bacteria selected between bacterial polysaccharides or detoxified lipopolysaccharides of different serological specificity.
Defined repeating carbohydrate epitopes and binding stoichiometry
Each carbohydrate structure comprises at least one repeating basic epitope consisting of a minimum of five to twelve monosaccharide residues, and at least one mole of carrier protein is bound to at least one mole of each of the at least three carbohydrate structure or their molar sum to form carried carbohydrate structures of different serological specificity in a physiologically acceptable vehicle.
Optional adjuvant or excipient in the administered vaccine
The method further includes administering the vaccine optionally together with a pharmaceutically acceptable adjuvant or excipient.
The inventive coverage centers on administering a multivalent glycoconjugate vaccine construct in which a Clostridium difficile helper-T dependent detoxified carrier is covalently bound to at least three carbohydrate structures of different serological specificity, where each carbohydrate carries repeating epitopes of at least five to twelve monosaccharide residues and where the carrier-to-carbohydrate binding is specified by molar binding constraints.
Stated Advantages
Reduced carrier protein burden and fewer injections compared to administering multiple monovalent conjugates.
Documented Applications
Protection of a subject from systemic and enteric infections due to at least one of the listed enteropathogenic bacteria, using a vaccine comprising the described antigenic multivalent molecular construct.
Targeting enteropathogenic bacteria including Clostridium difficile and multiple enteric bacteria, with a proposed parallel reduction of human norovirus gastroenteritis by targeting antibiotic-resistant bacterial hosts.
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