US2005208079A1PendingUtilityA1

Glucan-based vaccines

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Assignee: CASSONE ANTONIOPriority: May 15, 2002Filed: May 15, 2003Published: Sep 22, 2005
Est. expiryMay 15, 2022(expired)· nominal 20-yr term from priority
Inventors:Antonio CassoneLuciano Polonelli
A61P 43/00A61P 37/04A61P 27/02A61P 29/00A61P 33/08A61P 33/02A61P 31/00A61P 31/10A61P 31/04A61P 31/06A61P 1/04A61P 13/12A61P 11/04A61P 17/00C07K 16/14A61K 2039/55566C07K 17/10A61K 39/385A61K 2039/6037A61K 2039/521A61K 2039/505A61K 39/0002Y02A50/30
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Claims

Abstract

Anti-glucan antibodies have been found to be protective against systemic fungal infection with C. albicans , but the protective efficacy can be inhibited by blocking antibodies. The invention provides an immunogenic composition comprising a glucan and a pharmaceutically acceptable carrier, characterised in that, when administered to a mammalian recipient, the composition elicits protective anti-glucan antibodies but does not elicit antibodies which inhibit the protective efficacy of the anti-glucan anti-bodies. The glucan may be presented on the surface of a protease-treated microbial cell or may be presented as a protein-glucan conjugate. The glucan may be substituted by a glucan mimotope, a peptidomimetic of a glucan mimotope, or nucleic acid encoding a mimotope. Anti-glucan-antibodies show broad spectrum microbicidal activity. B-glucans are preferred, particularly those containing one or more B-1,6 linkages

Claims

exact text as granted — not AI-modified
1 . An immunogenic composition comprising an immunogenic component and a pharmaceutically acceptable carrier, wherein (a) the immunogenic component is a glucan, a mimotope of a glucan, a peptidomimetic of a glucan mimotope, or nucleic acid encoding a glucan mimotope, and (b) when the composition is administered to a mammal, it elicits protective anti-glucan antibodies but does not elicit antibodies which inhibit the protective efficacy of the anti-glucan antibodies.  
     
     
         2 . The composition of  claim 1 , wherein the glucan is a β-glucan.  
     
     
         3 . The composition of  claim 1  or  claim 2 , wherein the glucan contains one or more β-1,6-linkages.  
     
     
         4 . The composition of  claim 1 , wherein the glucan is a fungal glucan.  
     
     
         5 . The composition of  claim 1 , wherein the glucan is in the form of a protease-treated fungal cell.  
     
     
         6 . The composition of  claim 1 , wherein the glucan is in the form of a protein-glucan conjugate.  
     
     
         7 . The composition of  claim 2 , wherein the glucan is a β-glucan derived from the cell wall of a  Candida.    
     
     
         8 . The composition of  claim 1 , wherein the glucan has a molecular weight of less than 100 kDa.  
     
     
         9 . The composition of  claim 1 , wherein the composition is substantially free of mannoprotein.  
     
     
         10 . The composition of  claim 1 , further comprising an adjuvant.  
     
     
         11 . A composition comprising (1) antibody which recognises a glucan and (2) a pharmaceutically acceptable carrier.  
     
     
         12 . The composition of  claim 11 , wherein the glucan is a fungal β-glucan.  
     
     
         13 . The composition of  claim 12 , wherein the fungal β-glucan contains one or more β-1,6-linkages.  
     
     
         14 . A conjugate of (i) a carrier protein and (ii) a glucan.  
     
     
         15 . The conjugate of  claim 14 , wherein the glucan is a fungal β-glucan.  
     
     
         16 . The conjugate of  claim 15 , wherein the fungal β-glucan contains one or more β-1,6-linkages.  
     
     
         17 . The conjugate of  claim 14  or  claim 15  or  claim 16 , wherein the carrier protein is CRM197.  
     
     
         18 . A polypeptide comprising a mimotope of a fungal β-glucan.  
     
     
         19 . Nucleic acid that encodes the polypeptide of  claim 18 .  
     
     
         20 - 22 . (canceled)  
     
     
         23 . A method for raising an antibody response in a mammal, comprising administering a composition according to  claim 1  to the mammal.  
     
     
         24 . A method for treating or preventing a microbial infection in a mammal, comprising administering to the mammal a composition according to  claim 1 .  
     
     
         25 - 28 . (canceled)  
     
     
         29 . The method of  claim 23 , wherein the mammal is a human.  
     
     
         30 . The method of  claim 24 , wherein the microbial infection is caused by a species selected from the group consisting of:  Candida, Cryptococcus, Enterococcus, Streptococcus, Leishmania, Acanthamoeba, Aspergillus, Pneumocystis, Mycobacterium, Pseudomonas, Staphylococcus, Salmonella, Coccidioides, Trichophyton, Blastomyces, Histoplasma, Paracoccidioides, Pythiumn , and  Escherichia.    
     
     
         31 . The method of  claim 23 , wherein the microbial infection is selected from the group consisting of candidosis, aspergillosis, cryptococcosis, dermatomycoses, sporothrychosis and other subcutaneous mycoses, blastomycosis, histoplasmosis, coccidiomycosis, paracoccidiomycosis, pneumocystosis, thrush, tuberculosis, mycobacteriosis, respiratory infections, scarlet fever, pneumonia, impetigo, rheumatic fever, sepsis, septicaemia, cutaneous and visceral leishmaniasis, corneal acanthamoebiasis, cystic fibrosis, typhoid fever, gastroenteritis and hemolytic-uremic syndrome.  
     
     
         32 . The composition of  claim 1 , further comprising: a saccharide antigen from serogroups A, C, W135 and/or Y of  Neisseria meningitidis ; an antigen from  Helicobacter pylori ; a protein antigen from  N. meningitidis  serogroup B; an outer-membrane vesicle (OMV) preparation from  N. meningitidis  serogroup B; a saccharide antigen from  Streptococcus pneumoniae ; an antigen from hepatitis A virus; an antigen from hepatitis B virus; an antigen from hepatitis C virus; an antigen from  Bordetella pertussis ; a diphtheria antigen; a tetanus antigen; a saccharide antigen from  Haemophilus influenzae  B; an antigen from  N. gonorrhoeae ; an antigen from  Chlamydia pneumoniae ; an antigen from  Chlamydia trachomatis ; an antigen from  Porphyromonas gingivalis ; a polio antigen; a rabies antigen; a measles, mumps and/or rubella antigen; an antigen from influenza virus; an antigen from a paarmyxovirus such as respiratory syncytial virus or parainfluenza virus; an antigen from  Moraxella catarrhalis ; an antigen from  Streptococcus agalactiae ; an antigen from  Streptococcus pyogenes ; an antigen from  Staphylococcus aureus ; an antigen from  Bacillus anthracis ; an antigen from a virus in the flaviviridae family; a pestivirus antigen; a parvovirus antigen; a prion protein; an amyloid protein; and/or a cancer antigen.  
     
     
         33 . The composition of  claim 1 , further comprising an anti-fungal.  
     
     
         34 . A protease-treated fungal cell having surface-exposed β-glucans.  
     
     
         35 . The cell of  claim 34 , with a cell wall substantially free of mannoprotein.  
     
     
         36 . The composition of 7, wherein the glucan is a β-glucan derived from the cell wall of  C. albicans.    
     
     
         37 . A method for raising an antibody response in a mammal, comprising administering a composition according to  claim 11  to the mammal.  
     
     
         38 . A method for treating or preventing a microbial infection in a mammal comprising administering to the mammal a composition according to  claim 11 .  
     
     
         39 . The method of  claim 24 , wherein the mammal is a human.  
     
     
         40 . The method of  claim 37 , wherein the mammal is a human.  
     
     
         41 . The method of  claim 38 , wherein the mammal is a human.  
     
     
         42 . The method of  claim 38 , wherein the microbial infection is caused by a species selected from the group consisting of:  Candida, Cryptococcus, Enterococcus, Streptococcus, Leishmania, Acanthamoeba, Aspergillus, Pneumocystis, Mycobacterium, Pseudomonas, Staphylococcus, Salmonella, Coccidioides, Trichophyton, Blastomyces, Histoplasma, Paracoccidioides, Pythiumn , and  Escherichia.    
     
     
         43 . The method of  claim 38 , wherein the microbial infection is selected from the group consisting of candidosis, aspergillosis, cryptococcosis, dermatomycoses, sporothrychosis and other subcutaneous mycoses, blastomycosis, histoplasmosis, coccidiomycosis, paracoccidiomycosis, pneumocystosis, thrush, tuberculosis, mycobacteriosis, respiratory infections, scarlet fever, pneumonia, impetigo, rheumatic fever, sepsis, septicaemia, cutaneous and visceral leishmaniasis, corneal acanthamoebiasis, cystic fibrosis, typhoid fever, gastroenteritis and hemolytic-uremic syndrome.  
     
     
         44 . The composition of  claim 38 , further comprising: a saccharide antigen from serogroups A, C, W135 and/or Y of  Neisseria meningitidis ; an antigen from  Helicobacter pylori ; a protein antigen from  N. meningitidis  serogroup B; an outer-membrane vesicle (OMV) preparation from  N. meningitidis  serogroup B; a saccharide antigen from  Streptococcus pneumoniae ; an antigen from hepatitis A virus; an antigen from hepatitis B virus; an antigen from hepatitis C virus; an antigen from  Bordetella pertussis ; a diphtheria antigen; a tetanus antigen; a saccharide antigen from  Haemophilus influenzae  B; an antigen from  N. gonorrhoeae ; an antigen from  Chlamydia pneumoniae ; an antigen from  Chlamydia trachomatis ; an antigen from  Porphyromonas gingivalis ; a polio antigen; a rabies antigen; a measles, mumps and/or rubella antigen; an antigen from influenza virus; an antigen from a paarmyxovirus such as respiratory syncytial virus or parainfluenza virus; an antigen from  Moraxella catarrhalis ; an antigen from  Streptococcus agalactiae ; an antigen from  Streptococcus pyogenes ; an antigen from  Staphylococcus aureus ; an antigen from  Bacillus anthracis ; an antigen from a virus in the flaviviridae family; a pestivirus antigen; a parvovirus antigen; a prion protein; an amyloid protein; and/or a cancer antigen.  
     
     
         45 . The composition of  claim 11 , further comprising an anti-fungal.

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