Composition and method for the treatment and prevention of enteric bacterial infections
Inventors
Robins-Browne, Roy Michael • Rawlin, Grant Thomas • Lichti, Gottfried
Assignees
Publication Number
US-8637025-B2
Publication Date
2014-01-28
Expiration Date
2024-03-04
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Abstract
The present invention provides a method of treatment or prophylaxis of enteric disease caused by Gram negative bacteria. The method includes the step of administering a vaccine or a hyperimmune material raised against said vaccine to an individual. The vaccine comprises one or more cell wall antigens reactive in a manner characteristic of O group serotypes, or reactive in a manner characteristic of lipopolysaccharide associated antigens, and at least some of said antigens are separated from bacterial cell walls or wall fragments. The invention also provides composition containing hyperimmune material as well as uses of the composition and vaccine.
Core Innovation
The invention provides a method of treatment or prophylaxis of enteric disease caused by Gram negative bacteria by administering a vaccine or hyperimmune material raised against said vaccine to an individual. The vaccine comprises one or more cell wall antigens reactive in a manner characteristic of O group serotypes or lipopolysaccharide-associated antigens, with at least some of these antigens separated from bacterial cell walls or wall fragments.
The invention addresses the problem of gastrointestinal diseases such as diarrhoea caused by Gram negative bacteria including enterotoxigenic E. coli. Prior treatments such as antibiotics face issues like resistance and side effects, and symptomatic therapies fail to treat the cause. Existing vaccines using whole cell bacterial antigens produce large quantities of varied antibodies, many of which are not protective, and carry risks of adverse reactions limiting their use.
The innovation lies in immunising host animals with vaccines containing separated cell wall antigens, specifically O group serotype antigens separated from intact bacterial cell walls or fragments. This method enables production of hyperimmune materials like colostrum or egg yolk extracts containing targeted immunoglobulins. The invention also includes the processes for preparing and purifying such vaccines and hyperimmune materials, as well as their use in treating or preventing gastrointestinal diseases caused by Gram negative bacteria.
Claims Coverage
The patent contains one independent claim focused on a method for protection against enteric disease caused by Gram negative bacteria using antibodies derived from ungulate colostrum raised by vaccination with O group serotype antigens separated from bacterial cell walls.
Method for protection against enteric disease using colostrum-derived polyclonal antibodies
Providing O antigen derived polyclonal antibodies raised in ungulate colostrum by vaccination with O group serotype antigen prepared by shear separation from intact gram negative bacterial cell walls, and orally administering these antibodies to humans after removing whole cells and cell wall fragments by centrifugation.
Separation of antigen from gram negative bacteria by rotor-stator homogenisation
Using homogenisation in a rotor-stator setup with the peripheral speed to rotor-stator gap ratio between 0.2 to 20 to separate O antigen from bacterial cell walls.
Inclusion of specific Gram negative bacteria and E. coli strains
Using gram negative bacteria such as Helicobacter, Vibrio, Enterobacteriaceae, particularly E. coli strains including enterotoxigenic (ETEC), enterohaemorrhagic (EHEC), and enteropathogenic (EPEC), with O antigens from specific serogroups.
Purification of separated O antigens by ammonium sulphate precipitation
Purifying the separated O antigen using ammonium sulphate precipitation steps to remove extraneous proteins and concentrate antigens.
Inactivation of antigens using formaldehyde
Subjecting antigens separated from bacterial cell walls or fragments to formaldehyde inactivation.
Vaccination with specific adjuvants
Performing vaccination with adjuvants including esters of octodecenoic acid and anhydromannitol oily solutions, QuilA, or Aluminium Hydroxide.
Vaccine composition comprising at least two separated O antigens from distinct cultures
Comprising vaccines with at least two O antigens isolated and grown separately, then combined after separation from cell walls.
Inclusion of Colonization Factor Antigens CFA-1 and/or CFA-2
Including CFA pilus antigens separated from bacterial cell walls to enhance vaccine efficacy.
High quantity of CFA antigens dissociated from bacterial cell walls
Ensuring CFA antigens in the vaccine are present at quantities greater than those in bacterial cultures at 10⁶ or 10⁸ CFU/ml and that at least 20-40% of CFA proteins are dissociated from cell walls or fragments.
The independent claim covers a method of protecting humans from Gram negative enteric diseases by orally administering polyclonal antibodies derived from vaccinated ungulate colostrum with vaccines containing O group O antigens and optionally CFA antigens, prepared by separation from bacterial cell walls and purified accordingly.
Stated Advantages
Enhanced treatment or prophylaxis of enteric diseases caused by Gram negative bacteria through targeted vaccines and hyperimmune materials with improved antibody titres compared to whole-cell vaccines.
Reduced adverse vaccine reactions by using vaccines comprising separated cell wall antigens rather than whole cells.
Potential for production of hyperimmune colostrum or egg yolk extracts with high protective antibody concentrations.
Effective oral formulations able to confer protection against diarrhoea caused by enterotoxigenic E. coli in humans, including travellers' diarrhoea.
Documented Applications
Treatment and prophylaxis of gastrointestinal diseases caused by Gram negative bacteria including diarrhoea triggered by enterotoxigenic E. coli in humans and non-human animals.
Use of hyperimmune colostrum or egg yolk-derived immunoglobulins in oral formulations such as tablets, powders, syrups, or food additives for preventing or treating gastrointestinal dysfunction.
Vaccination of host animals like dairy cows with separated cell wall antigen vaccines to produce hyperimmune milk or eggs for therapeutic use.
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