Mycobacterium avium subspecies paratuberculosis oral vaccine and methods

Abstract

A method of orally immunizing a host organism against gastrointestinal, mucosally-invasive Mycobacterium avium subspecies paratuberculosis, including the steps of providing an enteric, mucosally-adherent, non-systemically invasive Mycobacterium avium subspecies paratuberculosis organism and orally administering the MAP organism to a host animal in an immunizing dose and manner. Also, a vaccine that includes such a Mycobacterium strain and a method of developing the strain.

1 . A method of orally immunizing a host animal against a gastrointestinal, mucosally invasive  Mycobacterium avium  subspecies paratuberculosis (MAP) the steps comprising: 
 a. providing an enteric, mucosally adherent, non-systemically invasive, live MAP organism having an attenuated virulence;    b. orally administering the MAP organism to a host animal in controlled dose and manner to elicit an immune response.    
     
     
         2 . The method of  claim 1 , wherein the MAP organism stimulates a Th1-type response and/or elicits IgA secretion and cell-mediated immunity.  
     
     
         3 . The method of  claim 2 , wherein the MAP is a viable organism.  
     
     
         4 . The method of  claim 2 , wherein the MAP is a recombinant organism.  
     
     
         5 . (cancelled without prejudice)  
     
     
         6 . The method of  claim 1 , wherein the MAP target organ is the intestinal mucosa.  
     
     
         7 . (cancelled without prejudice)  
     
     
         8 . (cancelled without prejudice)  
     
     
         9 . (cancelled without prejudice)  
     
     
         10 . (cancelled without prejudice)  
     
     
         11 . (cancelled without prejudice)  
     
     
         12 . (cancelled without prejudice)  
     
     
         13 . (cancelled without prejudice)  
     
     
         14 . (cancelled without prejudice)  
     
     
         15 . The method of  claim 1 , wherein the MAP organism is a serially passaged MAP strain.  
     
     
         16 . The method of  claim 1 , wherein the MAP organism has a modified adherence to the gastrointestinal mucosa of the host animal.  
     
     
         17 . The method of  claim 15 , wherein the MAP strain is selected on the basis of having a modified adherence to the gastrointestinal mucosa of the host animal.  
     
     
         18 . The method of  claim 15 , wherein the MAP strain is serially passaged in the presence of mutagens thereby increasing the probability of genetic variation produced during each round of passaging the MAP strain.  
     
     
         19 . The method of  claim 4 , wherein the recombinant MAP organism has a modified adherence to the gastrointestinal mucosa of the host animal.  
     
     
         20 . The method of  claim 1 , wherein the MAP is used in combination with a pharmaceutically acceptable carrier.  
     
     
         21 . The method of  claim 4 , wherein the recombinant MAP organism is used in combination with a pharmaceutically acceptable carrier.  
     
     
         22 . The method of  claim 15 , wherein the serially-passaged MAP strain is used in combination with a pharmaceutically acceptable carrier.  
     
     
         23 . The method of  claim 1 , wherein the oral administration of the attenuated MAP is used in combination with a killed MAP and/or an attenuated, live MAP that is parenterally administered.  
     
     
         24 . The method of  claim 4 , wherein the oral administration of the recombinant MAP organism is used in combination with a killed MAP and/or an attenuated, live MAP that is parenterally administered.  
     
     
         25 . The method of  claim 15 , wherein the oral administration of the serially passaged MAP strain is used in combination with a killed MAP and/or an attenuated, live MAP that are parenterally administered.  
     
     
         26 . A method of orally immunizing a host animal against a gastrointestinal, mucosally invasive  Mycobacterium avium  subspecies paratuberculosis (MAP), the steps comprising: 
 a. providing an enteric, mucosally adherent MAP organism;    b. killing the MAP organism by a non-protein denaturing process:    b. orally administering the killed MAP organism to a host animal in a controlled dose and manner to elicit an immune response.    
     
     
         27 . The method of  claim 26 , wherein the killed MAP has a modified binding affinity to the gastrointestinal mucosa of the host animal.  
     
     
         28 . The method of  claim 26 , wherein the killed MAP is used in combination with a pharmaceutically acceptable carrier.  
     
     
         29 . The method of  claim 26 , wherein the oral administration of the killed MAP is used in combination with a killed MAP and/or an attenuated, live MAP that are parenterally administered.  
     
     
         30 . The method of  claim 4 , wherein the recombinant MAP organism stimulates a Th1-type response and/or elicits IgA secretion and cell-mediated immunity.  
     
     
         31 . The method of  claim 15 , wherein the serially passaged MAP organism stimulates a Th1-type response and/or elicits IgA secretion and cell-mediated immunity.  
     
     
         32 . The method of  claim 26 , wherein the killed MAP stimulates a Th1-type response and/or elicits IgA secretion and cell-mediated immunity.  
     
     
         33 . The method of  claim 1 , wherein the controlled dose is that which elicits a interferon-γ response comparable to that observed in experimental animals when given between about 106 to about 108 colony forming units of a wild virulent strain of MAP.  
     
     
         34 . The method of  claim 16 , wherein the MAP organism has a lower than average adherence to the intestinal mucosa of the host animal.  
     
     
         35 . The method of  claim 19 , wherein the recombinant MAP organism has a lower than average adherence to the intestinal mucosa of the host animal.  
     
     
         36 . The method of  claim 17 , wherein the serially passaged MAP organism has a lower than average adherence to the intestinal mucosa of the host animal.  
     
     
         37 . The method of  claim 27 , wherein the killed MAP organism has a higher than average adherence to the intestinal mucosa of the host animal.  
     
     
         38 . The method of  claim 26 , wherein the controlled dose is that which elicits a interferon-γ response comparable to that observed in experimental animals when given between about 106 to about 108 colony forming units of a wild virulent strain of MAP.