Compositions and methods for treatment in broad-spectrum, undifferentiated or mixed clinical applications

Abstract

The disclosure provides improved compositions and methods for passive immunization. In embodiments, a composition comprising a synergistic combination of specific polyclonal antibodies in a carrier matrix is provided. The disclosure provides effective, economical compositions and methods for the treatment of diarrhea and enteric infections in broad-spectrum, undifferentiated, or mixed clinical applications.

1 . A dosage form comprising a composition for administration to a non-neonate human in need thereof, the composition comprising:
 a) a non-neonate effective amount of at least one antigen specific antibody, or antigen-binding fragment thereof, obtained from a first nonhuman animal; and,   b) a carrier matrix comprising colostrum, or at least two components thereof obtained from a second nonhuman animal, wherein the at least two components are selected from the group consisting of enzymes, lactoferrin, transferrin, nonspecific immunoglobulins, cytokines, white blood cells, complement components, interferons, growth factors, and fibronectin,
 wherein the at least one antigen-specific antibody or antigen-binding fragment thereof and the colostrum or the at least two components of the carrier matrix are obtained from different non-human animals. 
   
     
     
         2 . The dosage form of  claim 1 , wherein the carrier matrix comprises bovine colostrum. 
     
     
         3 . The composition of  claim 1 , wherein the at least two components of the carrier matrix are selected from the group consisting of lysozyme, phospholipase, defensins, opsonins, nonspecific immunoglobulins, proline-rich polypeptides (PRPs), components of the complement system, beta-lysin, lactoferrin, lactoperoxidase, transferrin, cytokines, interleukins, chemokines, interferons, TNF-alpha, fibronectin, leukocytes, white blood cells, phagocytes, macrophages, monocytes, neutrophils, polymorphonuclear cells, dendritic cells, mast cells, eosinophils, basophils, natural killer (NK) cells, lymphokine activated killer (LAK) cells, elastase, cathepsin G, myeloperoxidase, NADPH oxidase, insulin-like growth factor I, insulin-like growth factor II, transforming growth factor alpha, transforming growth factor beta 1, transforming growth factor beta 2, fibroblast growth factors, epidermal growth factor, granulocyte-macrophage stimulating growth factor, platelet-derived growth factor, vascular endothelial growth factor, colony-stimulating factor-I, leptin, hepatocyte growth factor, and combinations thereof. 
     
     
         4 . The dosage form of  claim 1 , wherein the antigen is present in or is derived from a bacterial or viral pathogen, a pathogen related toxin, a pathogen related adhesion element, undesirable strain, or a combination thereof. 
     
     
         5 . The dosage form of  claim 4 , wherein the bacterial or viral pathogen is a human or veterinary, enteric or gastrointestinal, pathogen capable of causing gastroenteritis. 
     
     
         6 . The dosage form of  claim 5 , wherein the bacterial or viral pathogen is selected from the group consisting of:  Campylobacter jejuni, Salmonella, Salmonella typhimurium, Salmonella enterica serovar Typhi, Shigella dystenteriae, Plesiomonas shigelloides, Escherichia coli , enteropathogenic  E. coli , enterotoxigenic  E. coli , enteroaggregative  E. coli , enteroinvasive  E. coli , haemorrhagic  E. coli, Clostridium difficile, Yersinia enterocolitica, Vibrio cholerae  O1,  Vibrio  O139, Non-O1  Vibrios, Vibrio parahaemolyticus, Aeromonas hydrophila, Clostridium perfringens , enterohepatic  Helicobacter, Helicobacter pylori, Staphylococcus aureus, Klebsiella, Gardnerella  spp.,  Neisseria gonorrhoeae, Chlamydiaceae trachomatis, Mycoplasma  spp.,  Campylobacter jejuni, Trichomonas vaginalis , herpes virus type 1, herpes virus type 2,  Candida albicans, Candida glabrata, Candida tropicalis, Candida parapsilosis  and  Candida krusei , Group A  Streptococcus  spp., rotavirus, coronavirus, norovirus, calicivirus, enteric adenovirus, cytomegalovirus, astrovirus,  S. pneumoniae, H. influenzae , herpes zoster virus,  Fusarium  spp., and  Acanthamoeba  spp. 
     
     
         7 . The dosage form of  claim 6 , wherein the at least one antigen-specific antibody, or antigen-binding fragment thereof comprise a mixture of polyclonal antibodies that are specific for one or more antigens present in the bacterial and/or viral pathogen, pathogen related toxin, or pathogen related adhesion element, derived from one, two, three, four, five, six, seven, or eight, or more, different pathogenic microorganisms. 
     
     
         8 . The dosage form of  claim 4 , wherein the pathogen related toxin comprises an endotoxin or exotoxin. 
     
     
         9 . The dosage form of  claim 4 , wherein the pathogen related adhesion element comprises adhesins, cadherins, cilia, fimbrillae, a viral adhesion structure, or a combination thereof. 
     
     
         10 . (canceled) 
     
     
         11 . The dosage form of  claim 1 , wherein the at least one antigen specific antibody or antigen-binding fragment thereof is selected from a mixture of polyclonal antibodies or a monoclonal antibody. 
     
     
         12 . The dosage form of  claim 11 , wherein the at least one antibody is an IgG. 
     
     
         13 . The dosage form of  claim 11 , wherein the at least one antibody is an IgY. 
     
     
         14 . The dosage form of  claim 11 , wherein the at least one antibody is a mixture of polyclonal antibodies. 
     
     
         15 . The dosage form of  claim 2 , wherein the bovine colostrum is non-hyperimmune bovine colostrum. 
     
     
         16 . The dosage form of  claim 2 , wherein the bovine colostrum is full fat bovine colostrum. 
     
     
         17 . The dosage form of  claim 1 , wherein the antigen specific antibody or antigen-binding fragment thereof is in a solid form. 
     
     
         18 . The dosage form of  claim 17 , wherein the antigen specific antibody or antigen-binding fragment thereof is crystalline. 
     
     
         19 . The dosage form of  claim 1 , wherein the carrier matrix is in a solid form. 
     
     
         20 . The dosage form of  claim 1  further comprising a pharmaceutically acceptable diluent, binder, excipient, lubricant, sweetening agent, flavoring agent, wetting agent, absorbent, and/or retarding agent. 
     
     
         21 .- 23 . (canceled) 
     
     
         24 . A method for the treatment or prevention of a pathogenic infection or undesirable strain of microorganisms in a non-neonate human in need thereof; the method comprising administration of a composition comprising:
 a) a non-neonate effective amount of at least one antigen specific antibody, or antigen-binding fragment thereof, obtained from a first nonhuman animal; and,   b) a carrier matrix comprising colostrum or at least two components thereof obtained from a second nonhuman animal, wherein the at least two components are selected from the group consisting of enzymes, lactoferrin, transferrin, nonspecific immunoglobulins, cytokines, white blood cells, complement components, interferons, growth factors, and fibronectin,   
       wherein the at least one antigen specific antibody or antigen-binding fragment thereof and the colostrum or at least two components of the carrier matrix are obtained from non-human different animals. 
     
     
         25 . The method of  claim 24 , wherein the pathogenic infection is selected from the group consisting of undifferentiated diarrhea, traveler's diarrhea, rotavirus diarrhea, toxin-mediated diarrhea, cholera,  C. difficile  infection, dysentery, typhoid fever, and peptic ulcers. 
     
     
         26 . The method of  claim 25 , wherein the undifferentiated diarrhea is pediatric undifferentiated diarrhea. 
     
     
         27 . The method of  claim 24 , wherein the composition is administered in an amount effective for conferring passive immunity to a subject. 
     
     
         28 . The method of  claim 24 , wherein the treatment or prevention of an undesirable strain of microorganisms is used for gastrointestinal flora management. 
     
     
         29 . The method of  claim 24 , wherein the pathogenic infection is caused by a microorganism selected from the group consisting of:  Campylobacter jejuni, Salmonella, Salmonella typhimurium, Salmonella enterica serovar Typhi, Shigella dystenteriae, Plesiomonas shigelloides, Escherichia coli , enteropathogenic  E. coli , enterotoxigenic  E. coli , enteroaggregative  E. coli , enteroinvasive  E. coli , haemorrhagic  E. coli, Clostridium difficile, Yersinia enterocolitica, Vibrio cholerae  O1,  Vibrio  O139, Non-O1  Vibrios, Vibrio parahaemolyticus, Aeromonas hydrophila, Clostridium perfringens , enterohepatic  Helicobacter, Helicobacter pylori, Staphylococcus aureus, Klebsiella, Gardnerella  spp.,  Neisseria gonorrhoeae, Chlamydiaceae trachomatis, Mycoplasma  spp.,  Campylobacter jejuni, Trichomonas vaginalis , herpes virus type 1, herpes virus type 2,  Candida albicans, Candida glabrata, Candida tropicalis, Candida parapsilosis  and  Candida krusei , Group A  Streptococcus  spp., rotavirus, coronavirus, norovirus, calicivirus, enteric adenovirus, cytomegalovirus, astrovirus,  S. pneumoniae, H. influenzae, Neisseria gonorrhoeae , herpes zoster virus,  Fusarium  spp., and  Acanthamoeba  spp. 
     
     
         30 . (canceled) 
     
     
         31 . The method of  claim 24 , wherein the colostrum is full fat bovine colostrum. 
     
     
         32 . The method of  claim 24 , wherein the colostrum is non-hyperimmune bovine colostrum. 
     
     
         33 . The method of  claim 24 , wherein the at least two components of the carrier matrix are selected from the group consisting of lysozyme, phospholipase, defensins, opsonins, nonspecific immunoglobulins, proline-rich polypeptides (PRPs), components of the complement system, beta-lysin, lactoferrin, lactoperoxidase, transferrin, cytokines, interleukins, chemokines, interferons, TNF-alpha, fibronectin, leukocytes, white blood cells, phagocytes, macrophages, monocytes, neutrophils, polymorphonuclear cells, dendritic cells, mast cells, eosinophils, basophils, natural killer (NK) cells, lymphokine activated killer (LAK) cells, elastase, cathepsin G, myeloperoxidase, NADPH oxidase, insulin-like growth factor I, insulin-like growth factor II, transforming growth factor alpha, transforming growth factor beta 1, transforming growth factor beta 2, fibroblast growth factors, epidermal growth factor, granulocyte-macrophage stimulating growth factor, platelet-derived growth factor, vascular endothelial growth factor, colony-stimulating factor-I, leptin, hepatocyte growth factor, and combinations thereof. 
     
     
         34 . The method of  claim 33 , wherein the at least two components of the carrier matrix include a growth factor and an antimicrobial factor. 
     
     
         35 . The method of  claim 24 , wherein the antigen is present in or is derived from a bacterial or viral pathogen, a pathogen related toxin, a pathogen related adhesion element, undesirable strain, or a combination thereof. 
     
     
         36 . The method of  claim 35 , wherein the bacterial or viral pathogen is a human or veterinary, enteric or gastrointestinal, pathogen capable of causing gastroenteritis. 
     
     
         37 . The method of  claim 36 , wherein the bacterial or viral pathogen is selected from the group consisting of:  Campylobacter jejuni, Salmonella, Salmonella typhimurium, Salmonella enterica serovar Typhi, Shigella dystenteriae, Plesiomonas shigelloides, Escherichia coli , enteropathogenic  E. coli , enterotoxigenic  E. coli , enteroaggregative  E. coli , enteroinvasive  E. coli , haemorrhagic  E. coli, Clostridium difficile, Yersinia enterocolitica, Vibrio cholerae  O1,  Vibrio  O139, Non-O1  Vibrios, Vibrio parahaemolyticus, Aeromonas hydrophila, Clostridium perfringens , enterohepatic  Helicobacter, Helicobacter pylori, Staphylococcus aureus, Klebsiella, Gardnerella  spp.,  Neisseria gonorrhoeae, Chlamydiaceae trachomatis, Mycoplasma  spp.,  Trichomonas vaginalis , herpes virus type 1, herpes virus type 2, Group A  Streptococcus  spp., rotavirus, coronavirus, norovirus, calicivirus, enteric adenovirus, cytomegalovirus, astrovirus,  S. pneumoniae, H. influenzae , herpes zoster virus. 
     
     
         38 . The method of  claim 37 , wherein the bacterial or viral pathogen is selected from the group consisting of  E. coli , rotavirus, and coronavirus. 
     
     
         39 . The method of  claim 37 , wherein the at least one antigen-specific antibody, or antigen-binding fragment thereof comprise a mixture of polyclonal antibodies that are specific for one or more antigens present in the bacterial and/or viral pathogen, pathogen related toxin, or pathogen related adhesion element, derived from one, two, three, four, five, six, seven, or eight, or more, different pathogenic microorganisms. 
     
     
         40 . The method of  claim 39 , wherein the mixture of polyclonal antibodies comprise IgY antibodies specific for at least enterotoxigenic  E. coli  spp.,  E. coli  K99 pili adherence factor,  Clostridium perfringens  toxoid,  Salmonella typhimurium , rotavirus, and coronavirus. 
     
     
         41 . The dosage form of  claim 1 , wherein the dosage form is in a form selected from the group consisting of powder, tablet, capsule, troche, or liquid. 
     
     
         42 . The dosage form of  claim 1 , wherein the dosage form is a solid dosage form. 
     
     
         43 . The dosage form of  claim 1 , wherein one dose of the composition comprises from 1 g to 7 g dried immune egg and from 1 g to 7 g dried bovine colostrum. 
     
     
         44 . The dosage form of  claim 1 , that is an oral dosage form.