Multivalent nanoemulsion vaccines

Abstract

The present invention provides methods and compositions for the stimulation of immune responses. Specifically, the present invention provides methods of inducing an immune response against one or a plurality of pathogens (e.g., vaccinia virus, H5N1 influenza virus, Bacillus anthracis, C. botulinum, Y. pestis , Hepatits B, and/or HIV, etc.) in a subject (e.g., a human subject) and compositions useful in such methods (e.g., immunogenic composition comprising nanoemulsion and one or a plurality of pathogens (e.g., inactivated by the nanoemulsion) and/or pathogen products and/or pathogen components). Compositions and methods of the present invention find use in, among other things, clinical (e.g. therapeutic and preventative medicine (e.g., vaccination)) and research applications

We claim: 
     
         1 . A method of inducing an immune response in a subject, comprising:
 a) providing a multivalent immunogenic composition comprising:
 (i) a nanoemulsion comprising:
 1) 30-90%, 60-80%, or 60-70% by volume oil; 
 2) 3-15% by volume solvent, wherein said solvent is selected from the group consisting of ethanol and glycerol; 
 3) 3-15% by volume surfactant, wherein said surfactant is selected from the group consisting of polyoxyethylenesorbitan monolaurate and polyoxyethylenesorbitan monooleate; 
 4) cetylpyridinium chloride (CPC); and 
 5) water; and 
 
 (ii) a plurality of different immunogens; and 
   b) administering the multivalent immunogenic composition to the subject under conditions such that the multivalent immunogenic composition concurrently induces an immune response specific to each of the plurality of different immunogens in the subject.   
     
     
         2 . The method of  claim 1 , wherein administering comprises contacting a nasal mucosal surface of the subject with the multivalent immunogenic composition. 
     
     
         3 . The method of  claim 1 , wherein the nanoemulsion comprises polyoxyethylenesorbitan monooleate, ethanol, and cetylpyridinium chloride (CPC). 
     
     
         4 . The method of  claim 1 , wherein the nanoemulsion comprises about 5 vol. % of polyoxyethylenesorbitan monooleate, about 8 vol. % of ethanol, about 1 vol. % of cetylpyridinium chloride (CPC), about 64 vol. % oil, and about 22 vol. % water. 
     
     
         5 . The method of  claim 1 , wherein the plurality of different immunogens are selected from the group consisting of inactivated pathogen, isolated protein or peptide, purified protein or peptide, and recombinant protein or peptide 
     
     
         6 . The method of  claim 1 , wherein the immune response comprises a systemic IgG response specific to each of the plurality of different immunogens. 
     
     
         7 . The method of  claim 1 , wherein the immune response comprises a mucosal IgA response specific to each of the plurality of different immunogens. 
     
     
         8 . The method of  claim 1 , wherein the immune response comprises a systemic IgG response specific to each of the plurality of different immunogens and a mucosal IgA response specific to each of the plurality of different immunogens. 
     
     
         9 . The method of  claim 1 , wherein the plurality of different immunogens are selected from the group consisting of virus, bacteria, fungus and pathogen products derived from said virus, bacteria, or fungus. 
     
     
         10 . The method of  claim 9 , wherein the virus is selected from the group consisting of 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 II, 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, and ebola virus. 
     
     
         11 . The method of  claim 9 , wherein the bacteria is selected from the group consisting of  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 , and  Yersinia pseudotuberculosis.