Microparticulated vaccines for the oral or nasal vaccination and boostering of animals including fish

Abstract

The invention relates to a composition and a method for manufacturing semi-dry or dry particles containing a mucoadhesive polymer and a bioactive agent such as, but not limited to, an Immunogenic Substance (e.g., a vaccine), that allows the oral or nasal administration and delivery of the bioactive agent essentially unaltered to mucosal surfaces in the animal, including an aquatic animal.

That which is claimed is: 
     
         1 . An immunogenic substance for oral or nasal vaccination comprising a vaccine, a cross-linked mucoadhesive polymer, 10-60 wt % of one or more sugars, 3-10 wt % of one or more oligosaccharides and 1-10 wt % of one or more electrolytes, wherein the immunogenic substance is prepared by a method comprising:
 (a) dissolving the mucoadhesive polymer and the one or more oligosaccharides in an aqueous solution;   (b) mixing the vaccine with the resulting solution from step (a) to form a slurry;   (c) cross-linking the mucoadhesive polymer in the slurry with the one or more electrolytes to form hydrogel particles;   (d) soaking the hydrogel particles in a solution saturated with the one or more sugars to make semi-dry particles; and   (e) drying the semi-dry particles to form the immunogenic substance.   
     
     
         2 . The immunogenic substance of  claim 1 , wherein the vaccine is a bacterin vaccine, a viral vaccine, or a recombinant vector that expresses a gene encoding an immunogenic protein. 
     
     
         3 . The immunogenic substance of  claim 1 , wherein the vaccine is selected from the group consisting of (a) recombinant vectors comprising a gene encoding an immunogenic protein, (b) intact inactive, attenuated or infectious viral particles, (c) intact killed, attenuated or infectious prokaryotes, (d) intact killed, attenuated or infectious protozoans, and (e) intact killed, attenuated or infectious multicellular pathogens. 
     
     
         4 . The immunogenic substance of  claim 1 , wherein the vaccine is against infectious salmon anemia virus (ISAV), Salmonid Rickettsial Septicaemia (SRS) or infectious pancreatic necrosis virus (IPNV). 
     
     
         5 . The immunogenic substance of  claim 1 , wherein the mucoadhesive polymer is a polysaccharide. 
     
     
         6 . The immunogenic substance of  claim 5 , wherein the polysaccharide is selected from the group consisting of chitosan, hyaluronic acid, alginate, cationic guar, and derivatives thereof. 
     
     
         7 . The immunogenic substance of  claim 1 , wherein the sugar is a monosaccharide or a disaccharide. 
     
     
         8 . The immunogenic substance of  claim 7 , wherein the disaccharide is selected from the group consisting of sucrose and trehalose. 
     
     
         9 . The immunogenic substance of  claim 1 , wherein the one or more electrolytes are one or more divalent or polyvalent cations or anions. 
     
     
         10 . The immunogenic substance of  claim 1 , wherein the one or more electrolytes are one or more salts of Ca, Zn, Al, triphosphate or hexametaphosphate. 
     
     
         11 . The immunogenic substance of  claim 1 , wherein the immunogenic substance consists of the vaccine, the cross-linked mucoadhesive polymer, the one or more sugars, the one or more oligosaccharides and the one or more electrolytes, wherein the one or more sugars are selected from the group consisting of fructose, sucrose, dextrose, and trehalose, wherein the one or more oligosaccharides are selected from the group consisting of inulin and fructooligosaccharides (FOS), and wherein the mucoadhesive polymer is a polymer that is not a dimer. 
     
     
         12 . The immunogenic substance of  claim 1 , wherein the immunogenic substance consists of the vaccine, the cross-linked mucoadhesive polymer, the one or more sugars, the one or more oligosaccharides, the one or more electrolytes, and an additional agent, wherein the one or more sugars are selected from the group consisting of fructose, sucrose, dextrose, and trehalose, wherein the one or more oligosaccharides are selected from the group consisting of inulin and fructooligosaccharides (FOS), and wherein the mucoadhesive polymer is a polymer that is not a dimer, and wherein the additional agent is selected from the group consisting of a phospholipid, beta glucan and a combination thereof. 
     
     
         13 . An animal feed comprising the immunogenic substance of  claim 1 . 
     
     
         14 . A method for vaccination of an animal, comprising administering the immunogenic substance of  claim 1  to the animal. 
     
     
         15 . The method of  claim 14 , wherein the animal is a fish, salmonid, bird or a mammal. 
     
     
         16 . The method of  claim 14 , wherein the vaccine is a bacterin vaccine, a viral vaccine, or a recombinant vector that expresses a gene encoding an immunogenic protein. 
     
     
         17 . The method of  claim 14 , wherein the vaccine is against infectious salmon anemia virus (ISAV), Salmonid Rickettsial Septicaemia (SRS) or infectious pancreatic necrosis virus (IPNV). 
     
     
         18 . The method of  claim 14 , wherein the immunogenic substance is spray coated on a feed pellet. 
     
     
         19 . The method of  claim 14 , wherein the immunogenic substance consists of the vaccine, the cross-linked mucoadhesive polymer, the one or more sugars, the one or more oligosaccharides and the one or more electrolytes, wherein the one or more sugars are selected from the group consisting of fructose, sucrose, dextrose, and trehalose, wherein the one or more oligosaccharides are selected from the group consisting of inulin and fructooligosaccharides (FOS), and wherein the mucoadhesive polymer is a polymer that is not a dimer. 
     
     
         20 . The method of  claim 14 , wherein the immunogenic substance consists of the vaccine, the cross-linked mucoadhesive polymer, the one or more sugars, the one or more oligosaccharides, the one or more electrolytes, and an additional agent, wherein the one or more sugars are selected from the group consisting of fructose, sucrose, dextrose, and trehalose, wherein the one or more oligosaccharides are selected from the group consisting of inulin and fructooligosaccharides (FOS), and wherein the mucoadhesive polymer is a polymer that is not a dimer, and wherein the additional agent is selected from the group consisting of a phospholipid, beta glucan and a combination thereof.