Target peptides for colorectal cancer therapy and diagnostics

Abstract

A set of target peptides are presented by HLA A*0201, B*0301, B*0702 and B*2705 on the surface of disease cells. They are envisioned to, among other things, stimulate an immune response to the proliferative disease, e.g., colorectal cancer, to function as immunotherapeutics in adoptive T cell therapy or as a vaccine, facilitate antibody recognition of tumor boundaries in surgical pathology samples, act as biomarkers for early detection and/or diagnosis of the disease, and/or act as targets in the generation antibody-like molecules which recognize the target-peptide/MHC complex.

1 - 41 . (canceled) 
     
     
         42 . A method of making a vaccine comprising synthesizing at least one target peptide with an amino acid sequence selected from the group consisting of:
 SEQ ID NO: 3, wherein the serine at the sixth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 5, wherein the serine at the third position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 6, wherein the serine at the sixth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 7, wherein the threonine at the fourth position is phosphorylated or replaced with a mimetic of phosphothreonine;   SEQ ID NO: 12, wherein the serine at the sixth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 13, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 14, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 15, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 20, wherein the threonine at the fifth position is phosphorylated or replaced with a mimetic of phosphothreonine;   SEQ ID NO: 22, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 24, wherein the serine at the fifth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 26, wherein the serine at the eighth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 28, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 29, wherein the serine at the fifth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 30, wherein the serine at the third position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 31, wherein the serine at the fifth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 32, wherein the serine at the eighth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 33, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 34, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 43, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 48, wherein the serine at the eighth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 49, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 50, wherein the serine at the ninth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 52, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 54, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 56, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 61, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 63, wherein the serine at the sixth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 67, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 68, wherein the serine at the ninth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 71, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 72, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 73, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 81, wherein the serine at the ninth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 85, wherein the serine at the seventh position of is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 87, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 91, wherein the serine at the eighth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 93, wherein the serine at the eighth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 94, wherein the serine at the sixth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 95, wherein the serine at the sixth position is phosphorylated or replaced with a mimetic of phosphoserine, the serine at the eighth position is phosphorylated or replaced with a mimetic of phosphoserine, or any combination thereof;   SEQ ID NO: 96, wherein the threonine at the fourth position is phosphorylated or replaced with a mimetic of phosphothreonine;   SEQ ID NO: 99, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 100, wherein the threonine at the sixth position is phosphorylated or replaced with a mimetic of phosphothreonine;   SEQ ID NO: 101, wherein the threonine at the sixth position is phosphorylated or replaced with a mimetic of phosphothreonine;   SEQ ID NO: 103, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 104, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 105, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 106, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 108, wherein the serine at the seventh position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 109, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 110, wherein the threonine at the fourth position is phosphorylated or replaced with a mimetic of phosphothreonine;   SEQ ID NO: 114, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 117, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 119, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine and the serine at the eighth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 123, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 126, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 128, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 129, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 131, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 132, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 135, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 140, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 141, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 143, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 144, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 146, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 147, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 148, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 149, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 150, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 154, wherein the serine at the third position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 155, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 157, wherein the serine at the fourth position of is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 158, wherein the serine at the sixth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 159, wherein the serine at the eighth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 160, wherein the serine at the fifth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 161, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 162, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 164, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 165, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 167, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 170, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 172, wherein the threonine at the fourth position is phosphorylated or replaced with a mimetic of phosphothreonine;   SEQ ID NO: 173, wherein the serine at the fifth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 174, wherein the serine at the sixth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 176, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine; and   SEQ ID NO: 177, wherein the threonine at the sixth position is phosphorylated or replaced with a mimetic of phosphothreonine.   
     
     
         43 . A method of inducing a cellular immune response to a target peptide in a subject, the method comprising administering to the subject an effective amount of a target peptide selected from the group consisting of:
 SEQ ID NO: 3, wherein the serine at the sixth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 5, wherein the serine at the third position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 6, wherein the serine at the sixth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 7, wherein the threonine at the fourth position is phosphorylated or replaced with a mimetic of phosphothreonine;   SEQ ID NO: 12, wherein the serine at the sixth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 13, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 14, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 15, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 20, wherein the threonine at the fifth position is phosphorylated or replaced with a mimetic of phosphothreonine;   SEQ ID NO: 22, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 24, wherein the serine at the fifth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 26, wherein the serine at the eighth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 28, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 29, wherein the serine at the fifth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 30, wherein the serine at the third position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 31, wherein the serine at the fifth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 32, wherein the serine at the eighth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 33, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 34, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 43, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 48, wherein the serine at the eighth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 49, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 50, wherein the serine at the ninth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 52, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 54, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 56, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 61, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 63, wherein the serine at the sixth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 67, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 68, wherein the serine at the ninth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 71, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 72, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 73, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 81, wherein the serine at the ninth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 85, wherein the serine at the seventh position of is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 87, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 91, wherein the serine at the eighth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 93, wherein the serine at the eighth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 94, wherein the serine at the sixth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 95, wherein the serine at the sixth position is phosphorylated or replaced with a mimetic of phosphoserine, the serine at the eighth position is phosphorylated or replaced with a mimetic of phosphoserine, or any combination thereof;   SEQ ID NO: 96, wherein the threonine at the fourth position is phosphorylated or replaced with a mimetic of phosphothreonine;   SEQ ID NO: 99, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 100, wherein the threonine at the sixth position is phosphorylated or replaced with a mimetic of phosphothreonine;   SEQ ID NO: 101, wherein the threonine at the sixth position is phosphorylated or replaced with a mimetic of phosphothreonine;   SEQ ID NO: 103, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 104, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 105, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 106, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 108, wherein the serine at the seventh position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 109, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 110, wherein the threonine at the fourth position is phosphorylated or replaced with a mimetic of phosphothreonine;   SEQ ID NO: 114, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 117, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 119, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine and the serine at the eighth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 123, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 126, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 128, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 129, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 131, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 132, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 135, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 140, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 141, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 143, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 144, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 146, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 147, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 148, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 149, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 150, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 154, wherein the serine at the third position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 155, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 157, wherein the serine at the fourth position of is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 158, wherein the serine at the sixth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 159, wherein the serine at the eighth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 160, wherein the serine at the fifth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 161, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 162, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 164, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 165, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 167, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 170, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 172, wherein the threonine at the fourth position is phosphorylated or replaced with a mimetic of phosphothreonine;   SEQ ID NO: 173, wherein the serine at the fifth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 174, wherein the serine at the sixth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 176, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine; and   SEQ ID NO: 177, wherein the threonine at the sixth position is phosphorylated or replaced with a mimetic of phosphothreonine.   
     
     
         44 . A kit comprising a first container containing at least one target peptide selected from group consisting of:
 SEQ ID NO: 3, wherein the serine at the sixth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 5, wherein the serine at the third position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 6, wherein the serine at the sixth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 7, wherein the threonine at the fourth position is phosphorylated or replaced with a mimetic of phosphothreonine;   SEQ ID NO: 12, wherein the serine at the sixth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 13, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 14, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 15, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 20, wherein the threonine at the fifth position is phosphorylated or replaced with a mimetic of phosphothreonine;   SEQ ID NO: 22, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 24, wherein the serine at the fifth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 26, wherein the serine at the eighth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 28, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 29, wherein the serine at the fifth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 30, wherein the serine at the third position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 31, wherein the serine at the fifth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 32, wherein the serine at the eighth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 33, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 34, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 43, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 48, wherein the serine at the eighth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 49, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 50, wherein the serine at the ninth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 52, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 54, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 56, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 61, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 63, wherein the serine at the sixth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 67, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 68, wherein the serine at the ninth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 71, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 72, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 73, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 81, wherein the serine at the ninth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 85, wherein the serine at the seventh position of is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 87, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 91, wherein the serine at the eighth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 93, wherein the serine at the eighth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 94, wherein the serine at the sixth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 95, wherein the serine at the sixth position is phosphorylated or replaced with a mimetic of phosphoserine, the serine at the eighth position is phosphorylated or replaced with a mimetic of phosphoserine, or any combination thereof;   SEQ ID NO: 96, wherein the threonine at the fourth position is phosphorylated or replaced with a mimetic of phosphothreonine;   SEQ ID NO: 99, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 100, wherein the threonine at the sixth position is phosphorylated or replaced with a mimetic of phosphothreonine;   SEQ ID NO: 101, wherein the threonine at the sixth position is phosphorylated or replaced with a mimetic of phosphothreonine;   SEQ ID NO: 103, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 104, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 105, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 106, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 108, wherein the serine at the seventh position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 109, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 110, wherein the threonine at the fourth position is phosphorylated or replaced with a mimetic of phosphothreonine;   SEQ ID NO: 114, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 117, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 119, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine and the serine at the eighth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 123, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 126, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 128, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 129, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 131, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 132, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 135, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 140, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 141, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 143, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 144, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 146, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 147, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 148, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 149, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 150, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 154, wherein the serine at the third position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 155, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 157, wherein the serine at the fourth position of is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 158, wherein the serine at the sixth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 159, wherein the serine at the eighth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 160, wherein the serine at the fifth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 161, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 162, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 164, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 165, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 167, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 170, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 172, wherein the threonine at the fourth position is phosphorylated or replaced with a mimetic of phosphothreonine;   SEQ ID NO: 173, wherein the serine at the fifth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 174, wherein the serine at the sixth position is phosphorylated or replaced with a mimetic of phosphoserine;   SEQ ID NO: 176, wherein the serine at the fourth position is phosphorylated or replaced with a mimetic of phosphoserine; and   SEQ ID NO: 177, wherein the threonine at the sixth position is phosphorylated or replaced with a mimetic of phosphothreonine; and   a second container containing an adjuvant.