Nanoemulsion Vaccines

Abstract

The present invention provides methods and compositions for the stimulation of immune responses. Specifically, the present invention provides methods and compositions for the use of nanoemulsion compounds as mucosal adjuvants to induce immunity against environmental pathogens. Accordingly, in some embodiments, the present invention provides nanoemulsion vaccines comprising a nanoemulsion and an inactivated pathogen or protein derived from the pathogen. The present invention thus provides improved vaccines against a variety of environmental and human-released pathogens.

1 . A composition for inducing an immune response to an immunogen in a subject comprising:
 a) a nanoemulsion, wherein said nanoemulsion comprises:
 1. oil; 
 2. a solvent; 
 3. a surfactant; and 
 4. water; 
   wherein the oil is soybean oil, avocado oil, squalene, olive oil, canola oil, corn oil, rapeseed oil, safflower oil, sunflower oil, or fish oil;   wherein the solvent is methanol, ethanol, propanol, octanol, glycerol, polyethylene glycol, or an organic phosphate based solvent;   wherein the surfactant is Polyethylene glycol tert-octylphenyl ether t-Octylphenoxypolyethoxyethanol 4-(1,1,3,3-Tetramethylbutyl)phenyl-polyethylene glycol (TRITON X-100); Polyoxyethylenesorbitan monolaurate, Polyethylene glycol sorbitan monolaurate (TWEEN 20); and 4-(1,1,3,3-Tetramethylbutyl)phenol polymer with formaldehyde and oxirane (TYLOXAPOL), an anionic surfactant or a nonionic surfactant; and   b) an immunogen, wherein the immunogen is influenza A virus, avian influenza virus, H5N1 influenza virus, West Nile virus, SARS virus, Marburg virus, Arenaviruses, Nipah virus, alphaviruses, filoviruses, herpes simplex virus I, herpes simplex virus TI, sendai virus, sindbis virus, vaccinia virus, parvovirus, human immunodeficiency virus, hepatitis B virus, hepatitis C virus, hepatitis A virus, cytomegalovirus, human papilloma virus, picornavirus, hantavirus, junin virus, ebola virus,  Bacillus cereus, Bacillus circulans  and  Bacillus megaterium, Bacillus anthracis , bacterial of the genus  Brucella, Vibrio cholera, Coxiella burnetii, Francisella tularensis, Chlamydia psittaci, Ricinus communis, Rickettsia prowazekii , bacteria of the genus  Salmonella, Cryptosporidium parvum, Burkholderia pseudomallei, Clostridium perfringens, Clostridium botulinum, Vibrio cholerae, Streptococcus pyogenes, Streptococcus agalactiae, Streptococcus pneumonia, Staphylococcus aureus, Neisseria gonorrhea, Haemophilus influenzae, Escherichia coli, Salmonella typhimurium, Shigella dysenteriae, Proteus mirabilis, Pseudomonas aeruginosa, Yersinia pestis, Yersinia enterocolitica, Yersinia pseudotuberculosis, Candida, Aspergillus, Fusarium, Trychophyton , pathogen product derived from virus, pathogen product derived from bacteria, or pathogen product derived from fungus;   
       wherein said composition is configured to induce an immune response to said immunogen when administered to said subject. 
     
     
         2 . The composition of  claim 1 , wherein said nanoemulsion further comprises a cationic halogen containing compound. 
     
     
         3 . The composition of  claim 2 , wherein said cationic halogen containing compound is selected from the group consisting of cetylpyridinium halides, cetyltrimethylammonium halides, cetyldimethylethylammonium halides, cetyldimethylbenzylammonium halides, cetyltributylphosphonium halides, dodecyltrimethylammonium halides, and tetradecyltrimethylammonium halides. 
     
     
         4 . The composition of  claim 3 , wherein said halide is selected from the group consisting of chloride, fluoride, bromide, and iodide. 
     
     
         5 . The composition of  claim 1 , wherein said nanoemulsion comprises a quaternary ammonium containing compound. 
     
     
         6 . The composition of  claim 5 , wherein said quaternary ammonium containing compound is selected from the group consisting of Alkyl dimethyl benzyl ammonium chloride, dialkyl dimethyl ammonium chloride, n-Alkyl dimethyl benzyl ammonium chloride, n-Alkyl dimethyl ethylbenzyl ammonium chloride, Dialkyl dimethyl ammonium chloride, and n-Alkyl dimethyl benzyl ammonium chloride. 
     
     
         7 . The composition of  claim 1 , wherein said nanoemulsion comprises 8% polyethylene glycol tert-octylphenyl ether t-Octylphenoxypolyethoxyethanol 4-(1,1,3,3-Tetramethylbutyl)phenyl-polyethylene glycol, 8% tributyl phosphate, 64% soybean oil, and 20% water. 
     
     
         8 . The composition of  claim 1 , wherein said nanoemulsion comprises 5% polyethylene glycol sorbitan monolaurate, 8% Ethanol; 1% cetylpyridinium chloride, 64% Soybean oil, and 22% water. 
     
     
         9 . The composition of  claim 1 , wherein said nanoemulsion comprises 1% cetylpyridinium chloride, 8% ethanol, 64% soybean oil, and 27% water. 
     
     
         10 . The composition of  claim 1 , wherein said nanoemulsion comprises 3% 4-(1,1,3,3-tetramethylbutyl)phenol polymer with formaldehyde and oxirane, 1% cetylpyridinium chloride, 8% ethanol, 64% soybean oil, and 24% water. 
     
     
         11 . The composition of  claim 1 , wherein said nanoemulsion comprises 4% polyethylene glycol tert-octylphenyl ether t-Octylphenoxypolyethoxyethanol 4-(1,1,3,3-Tetramethylbutyl)phenyl-polyethylene glycol, 8% ethanol, 64% soybean oil, and 24% water. 
     
     
         12 . The composition of  claim 1 , wherein said immunogen is stable for greater than four weeks in said nanoemulsion. 
     
     
         13 . The composition of  claim 1 , wherein said composition further comprises an adjuvant. 
     
     
         14 . The composition of  claim 1 , wherein said nanoemulsion comprises an oil phase distributed throughout the aqueous phase as droplets, wherein said droplets comprise a mean particle size of about 0.1 to 5 microns. 
     
     
         15 . The composition of  claim 1 , wherein said nanoemulsion comprises an oil phase distributed throughout the aqueous phase as droplets, wherein said droplets comprise a mean particle size of about 0.2-0.8 microns. 
     
     
         16 . The composition of  claim 1 , wherein said nanoemulsion comprises an oil phase distributed throughout the aqueous phase as droplets, wherein said nanoemulsion is formed by a process comprising blending said oil phase with said aqueous phase. 
     
     
         17 . The composition of  claim 16 , wherein said blending comprises blending said oil phase with an aqueous phase on a volume-to-volume ratio of about 4:1. 
     
     
         18 . A pharmaceutical composition comprising a composition of  claim 1  and a pharmaceutically acceptable carrier. 
     
     
         19 . The composition of  claim 18 , wherein said pharmaceutically acceptable carrier is selected from the group consisting of a liquid, cream, foam, lotion, and gel.