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

• US 9,623,094 B2
• Filed: 03/26/2010
• Issued: 04/18/2017
• Est. Priority Date: 03/27/2009
• Status: Active Grant

• Current Assignee: Advanced Bionutrition Corporation
• Original Assignee: Advanced Bionutrition Corporation
• Inventors: Harel, Moti, Carpenter, Brian
• Primary Examiner(s): Barham, Bethany
• Assistant Examiner(s): Lazaro, Dominic
• Application Number:
  US13/260,661
• Publication Number:
  US 20120040010A1
• Time in Patent Office: 2,580 Days
• Field of Search: None
• CPC Class Codes: A61K 2039/522 avirulent or attenuated
• CPC Class Codes: A61K 2039/5254 avirulent or attenuated
• CPC Class Codes: A61K 2039/5258 Virus-like particles
• CPC Class Codes: A61K 2039/541 Mucosal route
• CPC Class Codes: A61K 2039/542 oral/gastrointestinal
• CPC Class Codes: A61K 2039/543 intranasal
• CPC Class Codes: A61K 2039/552 Veterinary vaccine
• CPC Class Codes: A61K 2039/55555 Liposomes; Vesicles, e.g. nanoparticles; Spheres, e.g. nanospheres; Polymers
• CPC Class Codes: A61K 2039/55583 Polysaccharides
• CPC Class Codes: A61K 39/00 Medicinal preparations containing antigens or antibodies materials for immunoassay G01N33/53
• CPC Class Codes: A61K 39/0208 Specific bacteria not otherwise provided for
• CPC Class Codes: A61K 39/0233 Rickettsiales, e.g. Anaplasma
• CPC Class Codes: A61K 39/0241 Mollicutes, e.g. Mycoplasma, Erysipelothrix
• CPC Class Codes: A61K 39/12 Viral antigens
• CPC Class Codes: A61K 39/145 Orthomyxoviridae, e.g. influenza virus
• CPC Class Codes: A61K 39/21 Retroviridae, e.g. equine infectious anemia virus
• CPC Class Codes: A61K 39/39 characterised by the immunostimulating additives, e.g. chemical adjuvants
• CPC Class Codes: A61K 9/0043 Nose
• CPC Class Codes: A61K 9/006 Oral mucosa, e.g. mucoadhesive forms, sublingual droplets; Buccal patches or films; Buccal sprays
• CPC Class Codes: A61K 9/5015 Organic compounds, e.g. fats, sugars
• CPC Class Codes: A61P 31/00 : Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 31/14 : for RNA viruses
• CPC Class Codes: A61P 37/00 : Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/04 : Immunostimulants
• CPC Class Codes: C12N 2720/10011 : Birnaviridae
• CPC Class Codes: C12N 2720/10023 : Virus like particles [VLP]
• CPC Class Codes: C12N 2720/10034 : Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
• CPC Class Codes: C12N 2740/10011 : Retroviridae
• CPC Class Codes: C12N 2740/10034 : Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
• CPC Class Codes: C12N 2760/10034 : Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
• CPC Class Codes: C12N 2760/16011 : Orthomyxoviridae
• CPC Class Codes: C12N 2760/16022 : New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
• CPC Class Codes: C12N 2760/16034 : Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
• CPC Class Codes: C12N 7/00 : Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof preparing medicinal viral antigen or antibody compositions, e.g. virus vaccines, A61K39/00

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.

Claims

1. A method of preparing an immunogenic substance suitable for oral or nasal vaccination, wherein the immunogenic substance consists of a vaccine, a crosslinked mucoadhesive polymer, one or more sugars, one or more oligosaccharides and 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 frutcoologosaccharides (FOS), and

wherein the mucoadhesive polymer is a polymer that is not a dimer,

the method comprising:

(a) dissolving a 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 one or more sugars to make semi-dry particles; and

(e) drying the semi-dry particles, whereby the immunogenic substance is formed.

2. The method 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 method of claim 1, wherein the mucoadhesive polymer is a polysaccharide.

4. The method of claim 3, wherein the polysaccharide is selected from the group consisting of chitosan, hyaluronic acid, alginate, cationic guar, and derivatives thereof.

5. The method of claim 1, wherein the sugar is a monosaccharide or a disaccharide.

6. The method of claim 5, wherein the disaccharide is selected from the group consisting of sucrose and trehalose.

7. The method of claim 1, wherein the one or more electrolytes are one or more divalent or polyvalent cations or anions.

8. The method of claim 1, wherein the one or more electrolytes are one or more salts of Ca, Zn, Al, triphosphate or hexametaphosphate.

9. The method of claim 1, wherein the vaccine is selected from the group consisting of (a) recombinant vectors containing a gene encoding an immunogenic protein, (b) intact inactive, attenuated and infectious viral particles, (c) intact killed, attenuated and infectious prokaryotes, (d) intact killed, attenuated and infectious protozoans, and (e) intact killed, attenuated and infectious multicellular pathogens.

10. The method of claim 1, wherein the vaccine is against infectious salmon anemia virus (ISAV), Salmonid Rickettsial Septicaemia (SRS) or infectious pancreatic necrosis virus (IPNV).

11. The method of claim 1, further comprising blending the immunogenic substance with oil and top-coating feed pellets.

12. The method of claim 11, further comprising spray coating the immunogenic substance on the feed pellets.

13. The method of claim 1, further comprising:

(f) incorporating the immunogenic substance into a feed formula, and

(g) pelleting or extruding the resulting feed formula from step (f), whereby a dry feed pellet containing the immunogenic substance is formed.

14. The method of claim 1, wherein the vaccination is oral.

15. The method of claim 1, wherein the vaccination is nasal.

16. The method of claim 1, further comprising freeze drying or spray drying the immunogenic substance, whereby a dry immunogenic powder is formed.

17. The method of claim 1, wherein the semi-dry particles have a moisture content of 10-20%.

18. The method of claim 1, wherein the mucoadhesive polymer is chitosan and the one or more electrolytes contain a soluble phosphate salt.

19. The method of claim 1, wherein the mucoadhesive polymer is alginate and the one or more electrolytes contain a soluble calcium salt.

20. The method of claim 1, wherein the immunogenic substance contains the one or more sugars at 10-60 wt %, the one or more oligosaccharides at 3-10 wt %, and the one or more electrolytes at 1-10 wt %.

21. A method of preparing an immunogenic substance suitable for oral or nasal vaccination,

wherein the immunogenic substance consists of a vaccine, a cross-linked mucoadhesive polymer, one or more sugars, one or more oligosaccharides, one or more electrolytes, and an additional agent selected from the group consisting of a phospholipid, beta glucan and a combination thereof,

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,

the method comprising:

(a) dissolving a 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) adding the additional agent to the aqueous solution of step (a) or the slurry of step (b);

(d) cross-linking the mucoadhesive polymer in the slurry with the one or more electrolytes to form hydrogel particles;

(e) soaking the hydrogel particles in a solution saturated with one or more sugars to make semi-dry particles; and

(f) drying the semi-dry particles, whereby the immunogenic substance is formed.

22. The method of claim 21, wherein the additional agent is a phospholipid, wherein the phospholipid is lecithin.