Novel vaccines and pharmaceutical compositions using membrane vesicles of microorganisms, and methods for preparing same

Abstract

The invention relates to novel vaccines and pharmaceutical compositions using membrane vesicles of microorganisms, methods for preparing same, and their use in the prevention and treatment of infectious diseases.

We claim:  
     
         1 . A vaccine against an infectious disease caused by an infectious agent comprising a carrier strain having a membrane vesicle of a microorganism integrated into the cell surface of the carrier strain, wherein the membrane vesicle has an amount of an antigen associated with its surface which is effective to provide protection against the infectious agent.  
     
     
         2 . A vaccine as claimed in  claim 1  wherein the infectious agent is a microorganism which produces membrane vesicles.  
     
     
         3 . A vaccine as claimed in  claim 2  wherein the microorganism is  Pseudomonas aeruginosa, Escherichia coli, Salmonella gastroenteritis  ( typhimirium ),  S. typhi, S. enteriditis, Shigella flexneri, S. sonnie, S dysenteriae, Neisseria gonorrhoeae, N. meningitides, Haemophilus, influenzae H. pleuropneumoniae, Pasteurella haemolytica, P. multilocida, Legionella pneumophila, Treponema pallidum, T. denticola, T. orale, Borrelia burgdorferi,  Borrelia spp.  Leptospira interrogans, Klebsiella pneumoniae, Proteus vulgaris, P. morganii, P. mirabilis, Rickettsia prowazeki, R.typhi, R. richettsii, Porphyromonas  (Bacteriodes)  gingivalis, Chlamydia psittaci, C. pneumoniae, C. trachomatis, Campylobacter jejuni, C. intermedis, C. fetus, Helicobacter pylori, Francisella tularenisis, Vibrio cholerae, Vibrio parahaemolyticus, Bordetella pertussis, Burkholderie pseudomallei, Brucella abortus, B. susi, B. melitensis, B. canis, Spirillum minus, Pseudomonas mallei, Aeromonas hydrophila, A salmonicida,  and  Yersinia pestis.    
     
     
         4 . A vaccine as claimed in  claim 2 , wherein the membrane vesicle is a natural membrane vesicle of the microorganism containing outer membrane and periplasm components.  
     
     
         5 . A vaccine as claimed in  claim 2  wherein the membrane vesicle is a large membrane vesicle which is obtained by treating the microorganism with a surface-active agent, and is characterized by containing outer membrane, cytoplasmic membrane or plasma membrane, and cytoplasm components.  
     
     
         6 . A vaccine as claimed in  claim 1  which is effective against another infectious agent comprising a second carrier strain having a membrane vesicle of a microorganism integrated into the cell surface of the second carrier strain, wherein the membrane vesicle has an amount of an antigen associated with its surface which is effective to provide protection against the other infectious agent.  
     
     
         7 . A pharmaceutical composition comprising a membrane vesicle of a microorganism containing one or more enzymes with peptidoglycan hydrolase, lipase and proteolytic activity in an amount effective to have a bactericidal effect on gram-negative and/or gram-positive bacterial pathogens, and a pharmaceutically acceptable vehicle or diluent.  
     
     
         8 . A pharmaceutical composition as claimed in  claim 7  which additionally contains a therapeutic agent.  
     
     
         9 . A pharmaceutical composition as claimed in  claim 8  wherein the therapeutic agent is an antimicrobial agent or an antiviral agent.  
     
     
         10 . A pharmaceutical composition as claimed in  claim 9  wherein the therapeutic agent is an aminoglycoside.  
     
     
         11 . A pharmaceutical composition as claimed in  claim 7  additionally comprising membrane vesicles of another microorganism, containing one or more enzymes with peptidoglycan hydrolase, lipase and proteolyfic activity in amounts effective to have a bactericidal effect on gram-negative and/or gram-positive bacterial pathogens.  
     
     
         12 . A method of treating an infectious disease caused by a gram-negative and/or gram-positive bacterial pathogen comprising administering an amount of a pharmaceutical composition as claimed in  claim 7  effective to have a bactericidal effect on the gram-negative and/or gram-positive bacterial pathogen.  
     
     
         13 . A drug delivery system comprising a membrane vesicle of a microorganism containing a therapeutic agent in an amount effective to introduce the therapeutic agent into a host.  
     
     
         14 . A drug delivery system as claimed in  claim 13  wherein the therapeutic agent is an antimicrobial agent or an antiviral agent.  
     
     
         15 . A method of inserting a nucleic acid molecule into a target cell which comprises encapsulating the nucleic acid in a membrane vesicle of a microorganism, and bringing the membrane vesicle in contact with the tat cell whereby the nucleic acid molecule is inserted into the cell.  
     
     
         16 . A method as claimed in  claim 15 , wherein the nucleic acid molecule encodes a protein which is endogenous or exogenous to the microorganism.  
     
     
         17 . A method as claimed in  claim 15  wherein the nucleic acid molecule encodes a mammalian protein, viral protein, fungal protein or protozoal protein.