Vaccine Compositions for Inducing Immune Responses Against Components of Drusen

Abstract

Disclosed are compositions and methods for treating or preventing the formation of drusen in a patient in need thereof. The compositions include an effective amount of at least one polypeptide present in drusen, or an immunogenic fragment or variant thereof that induces an immune response against the polypeptide, together with a pharmaceutical carrier, excipient, or diluent. The compositions are suitable as vaccines for treating or preventing drusen and diseases associated with drusen.

1 . A vaccine composition for treating or preventing drusen in a patient in need thereof, the composition comprising:
 (a) an effective amount of at least one polypeptide present in drusen or an immunogenic fragment or variant of the polypeptide, wherein the amount is effective for stimulating an immune response against the polypeptide after the vaccine composition is administered to the patient; and   (b) a pharmaceutical carrier, excipient, or diluent.   
     
     
         2 . The vaccine composition of  claim 1 ., further comprising an adjuvant. 
     
     
         3 . The vaccine composition according to  claim 1 , wherein the polypeptide is selected from a group consisting of histone H1, histone H2A, histone H 2 B, histone H2AC, histone H2AZ, histone H2A/O, histone H2A2, histone H 2 BF, histone h2bc, histone H3, histone H4, aldehyde dehydrogenase 3, aldehyde dehydrogenase 5, ATP synthase α-chain of mitochondria, cell adhesion protein SQM1, creatine kinase B, enolase 2, aldolase A, malate dehydrogenase 1, pyruvate dehydrogenase, pyruvate kinase, recoverin, lactate dehydrogenase A, protein kinase inhibitor β, glucose phosphate isomerase, cyclophilin A, phosphoglycerate kinase, calmodulin 2, G3PDH, dystrobrevin α, phosphoinositide-3-kinase, triosephosphate isomerase 1, 14-3-3 β, apolipoprotein A1, phospholipase A2, myosin, β S -crystallin, α-B-crystallin, β-A3-crystallin, β-A4-crystallin, β-B1-crystallin, β-B2-crystallin, polyubiquitin, ubiquitin, peroxiredoxin, VEGF, retinoic acid binding protein 3, calrecticulin, calrecticulin precursor, CD63, CD81, LAMP-2, actin β, actinin α, vimentin, plectin 1, actin a2, tubulin α1a, tubulin, α3, tubulin β, and combinations thereof. 
     
     
         4 . The vaccine composition according to  claim 1 , wherein the polypeptide is a crystallin protein. 
     
     
         5 . The vaccine composition according to  claim 4 , wherein the crystallin protein is selected from the group consisting of β S -crystallin, α-B-crystallin, β-A3-crystallin, β-A4-crystallin, β-B1-crystallin, β-B2-crystallin, and combinations thereof. 
     
     
         6 . The vaccine composition according to  claim 1 , wherein the at least one polypeptide is β S -crystallin. 
     
     
         7 . The vaccine composition according to  claim 1 , wherein the at least one polypeptide is α-B-crystallin. 
     
     
         8 . The vaccine composition according to  claim 1  wherein the at least one polypeptide is vimentin. 
     
     
         9 . The vaccine composition according to  claim 1 , wherein the at least one polypeptide is calreticulin precursor. 
     
     
         10 . The vaccine composition according to  claim 1 , wherein the at least one polypeptide is cyclophilin A. 
     
     
         11 . The vaccine composition according to  claim 1 , wherein the immune response is an antibody response. 
     
     
         12 . The vaccine composition according to  claim 1 , wherein the vaccine composition is effective for preventing the formation of drusen after the vaccine composition is administered to the patient. 
     
     
         13 . A method for treating or preventing drusen in a patient in need thereof, the method comprising administering the vaccine composition of  claim 1  to the patient in a manner effective for stimulating an immune response against the polypeptide of the vaccine. 
     
     
         14 . The method of  claim 13 , wherein the vaccine is administered under a prime-boost vaccination regimen. 
     
     
         15 . A method for inhibiting accumulation of drusen proteins extracellularly in the region of the retinal pigment epithelium and choroid of a patient in need thereof, the method comprising administering the vaccine composition of  claim 1  to the patient in a manner effective for stimulating an immune response against the polypeptide of the vaccine. 
     
     
         16 . The method of  claim 15 , wherein the vaccine is administered under a prime-boost vaccination regimen. 
     
     
         17 . A method for treating or preventing macular degeneration in a patient in need thereof, the method comprising administering the composition of  claim 1  to the patient in a manner effective for stimulating an immune response against the polypeptide of the vaccine. 
     
     
         18 . The method of  claim 17 , wherein the vaccine is administered under a prime-boost vaccination regimen. 
     
     
         19 . The method of  claim 17 , wherein the patient has dry AMD. 
     
     
         20 . The method of  claim 17 , wherein the patient has wet AMD.