Processes for production of immunoglobulin a in milk

Abstract

The present invention provides a process for producing immunoglobulin A in the milk of hyperimmunised ruminants using a 3 route immunisation protocol and uses for the resultant product. These products are useful in producing formulations useful for passive immunisation against selected pathogens, especially in preparations for food products and dietary preparations.

1 . A process for the induction of immunoglobulin A (IgA) in a mammal which process comprises: 
 (a) actively immunising a pregnant mammal with an antigen by any two routes of administration selected from the intramammary (IMM), intraperitoneal (IP) and intramuscular (IM); and    (b) actively immunising said mammal with an antigen by a third administration route selected from intramammary (IMM), intraperitoneal (IP) and intramuscular (IM); with the proviso that all three administration routes are different.    
     
     
         2 . A process according to  claim 1  wherein in step (a) the two routes of administration selected are IP and IM and in step (b) the third route of administration is IMM.  
     
     
         3 . A process according to  claim 1  or  claim 2  wherein the two active immunisations of step (a) are effected sequentially, discontinuously or concurrently.  
     
     
         4 . A process according to  claim 3  wherein the two active immunisations of step (a) are effected concurrently.  
     
     
         5 . A process according any one of  claims 1  to  4  wherein steps (a) and (b) are effected sequentially, discontinuously or concurrently.  
     
     
         6 . A process according to any one of  claims 1  to  5  wherein steps (a) and (b) are repeated once or twice prior to parturition.  
     
     
         7 . A process according to any one of  claims 1  to  5  wherein step (a) is repeated twice, prior to parturition.  
     
     
         8 . A process according to  claim 7  wherein each step (a) is effected at 2 to 8 week intervals.  
     
     
         9 . A process according to  claim 8  wherein each step (a) is effected at 2 to 4 week intervals.  
     
     
         10 . A process according to any one of  claims 6  to  9  wherein step (a) is effected 6 to 14 weeks prior to parturition, first repeat step (a) at 2 to 10 weeks prior to parturition, and the final step (a) at 1 to 4 weeks prior to parturition.  
     
     
         11 . A process according to  claim 10  wherein step (a) is effected 8 to 12 weeks prior to parturition, first repeat step (a) at 4 to 8 weeks prior to parturition, and the final step (a) at 1 to 4 weeks prior to parturition.  
     
     
         12 . A process according to  claim 11  wherein step (a) is effected 8 weeks prior to parturition, first repeat step (a) at 4 weeks prior to parturition, and the final step (a) at 1 week prior to parturition.  
     
     
         13 . A process according to any one of  claims 6  to  12  wherein step (b) is repeated once prior to parturition.  
     
     
         14 . A process according to any one of  claims 6  to  13  wherein the (b) steps are effected at 1 to 6 week intervals.  
     
     
         15 . A process according to  claim 14  wherein the (b) steps are effected at 2 week intervals.  
     
     
         16 . A process according to  claim 13  or  claim 14  wherein step (b) is effected 3 to 12 weeks prior to parturition, and repeat step (b) at 1 to 10 weeks prior to parturition.  
     
     
         17 . A process according to  claim 16  wherein step (b) is effected 4 to 8 weeks prior to parturition and repeat step (b) 2 to 4 weeks prior to parturition.  
     
     
         18 . A process according to  claim 17  wherein step (b) is effected 4 weeks prior to parturition and repeat step (b) at 2 weeks prior to parturition.  
     
     
         19 . A process for the production of mammalian milk containing immunoglobulin A (IgA), which process comprises: 
 (a) induction of IgA according to the process of any one of  claims 1  to  18 ; and    (b) collecting milk containing IgA from said mammal.    
     
     
         20 . A process according to any one of  claims 1  to  19  wherein the antigen comprises at least one of the group of bacteria, yeasts, viruses, mycoplasmas, proteins, haptens, animal tissue extracts, plant tissue extracts, spermatozoa, fungi, pollens, dust and a complex of antigens.  
     
     
         21 . A process according to  claim 20  wherein the antigen is a bacterial antigen.  
     
     
         22 . A process according to  claim 21  wherein the bacterial antigen is selected from the group consisting of Escherichia, Staphylococcus, Streptococcus, Salmonella, Pneumonococcus, Helicobacter, Cryptosporidiosus, Campylobacter and Shigella.  
     
     
         23 . A process according to  claim 22  wherein the bacterial antigen is  E. coli.    
     
     
         24 . A process according to  claim 20  wherein the antigen is a yeast antigen.  
     
     
         25 . A process according to  claim 24  wherein the yeast is  Candida albicans.    
     
     
         26 . A process according to  claim 20  wherein the antigen is a protein antigen.  
     
     
         27 . A process according to  claim 26  wherein the protein antigen is tumour necrosis factor.  
     
     
         28 . A process according to  claim 20  wherein the antigen is a complex of antigens.  
     
     
         29 . A process according to  claim 28  wherein the complex of antigens comprises  E. coli , rotavirus and coronavirus.  
     
     
         30 . A process according to any one of  claims 1  to  29  wherein the antigen is formulated as a suspension.  
     
     
         31 . A process according to any one of  claims 1  to  30  wherein the antigen is administered together with an acceptable carrier, diluent, buffer, and/or adjuvant.  
     
     
         32 . A process according to  claim 31  wherein the antigen is administered together with an adjuvant.  
     
     
         33 . A process according to  claim 32  wherein the adjuvant is selected from Freund's complete adjuvant (FCA), Freund's incomplete adjuvant (FIC) adjuvant 65, cholera toxin B subunit, alhydrogen; or  bordetella pertussis , muramyl dipeptide, cytokinins and saponin. Oil based adjuvants and in particular FCA and FIC are preferred  
     
     
         34 . A process according to  claim 33  wherein the adjuvant is Freunds incomplete adjuvant.  
     
     
         35 . A process according to any one of  claims 1  to  34  wherein the antigen is administered together with an antibiotic.  
     
     
         36 . A process according to any one of  claims 1  to  35  wherein the antigen administered in each immunising process, and at each site, is the same or different.  
     
     
         37 . A process according to  claim 36  wherein the antigen administered in each immunising process, and at each site, is the same.  
     
     
         38 . The process according to any one of  claims 1  to  37  wherein the mammal immunised is selected from the group consisting of cows, goats and sheep.  
     
     
         39 . A process according to  claim 38  wherein the mammal is a diary cow.  
     
     
         40 . IgA produced in accordance with the process of any one of  claims 1  to  39 .  
     
     
         41 . A process for the production of mammalian milk containing IgA, which process comprises: 
 (a) induction of IgA according to the process of any one of  claims 1  to  39 ; and    (b) collecting milk containing said IgA from said mammal.    
     
     
         42 . IgA containing mammaliam milk produced in accordance with the process of  claim 41 .  
     
     
         43 . IgA isolated from the mammalian milk of  claim 42 .  
     
     
         44 . The IgA of  claim 43  which is purified IgA.  
     
     
         45 . Use of the IgA of  claim 40  or  claim 44  as, or in the preparation of, pharmaceutical, cosmetic, and/or veterinary compositions.  
     
     
         46 . Use of the IgA of any one of  claims 42  to  44  as, or in the preparation of, food products and/or dietary supplements.