The Classification and Origins of Protein Folding Patterns

Recombinant Allergens with Reduced Allergenicity but Retaining Immunogenicity of the Natural Allergens: Hybrids of Yellow Jacket and Paper Wasp Venom Allergen Antigen 5s

“…The homologous host protein functions as a scaffold to maintain the native structure of the guest allergen of interest so that the conformation-dependent B cell epitopes of the guest allergen of interest are preserved in the hybrid, but at a reduced density. Homologous proteins of Ͼ30% sequence identity and of similar functions are known to have closely similar threedimensional structures (16,17).…”

“…At the highest concentration of 50 or 500 g/ml inhibitor tested, the two N-terminal hybrids, EA-PV 1-46 and EA-PV 1-155 , showed maximal inhibition approaching 100%, as EA-or KR-Ves v 5 did. Two other N-terminal hybrids, KR-PV and EA-PV , had maximal inhibition of ϳ60%, and the shortest N-terminal hybrid, EA-PV [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18] , had maximal inhibition of ϳ20%. The C-terminal hybrid EA-PV 156 -204 had maximal inhibition of ϳ15%, and the shorter C-terminal hybrid, EA-PV 195-204 , was not tested.…”

“…The high concentrations of hybrids required for half-maximal inhibition relative to that of Ves v 5 are probably related to their epitope densities, because epitope density is known to strongly influence the affinity constant of a multivalent Ag and a bivalent Ab (28,29). This may explain why the longest N-terminal hybrid, PV , showed the lowest concentration for half-maximal inhibition, and it is followed by the next longest hybrids, PV , PV , PV , and PV [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18] .…”

“…The data in set A of Table III indicate that, of the three N-terminal hybrids, PV 1-155 was as immunogenic as Ves v 5 was, PV 1-46 was half as imunogenic, and PV 1-18 was approximately one-ninth as immunogenic. The data in set B indicate that PV and PV were more immunogenic than PV 1-24 and PV [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18] . More importantly, the data from both sets suggest that the longer N-terminal hybrids PV and PV 1-32 stimulate higher contents of Ves v 5-specific Abs and lower contents of Pol a 5-specific Abs than the two shorter hybrids, PV and PV [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18] , did.…”

“…EA-PV and EA-PV [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18] showed geometric mean reductions of 126-and 583-fold, respectively, in group A patients and 0.7-and 24-fold decreases, respectively, in group B patients. The two C-terminal hybrids, EA-PV 156 -204 and EA-PV [195][196][197][198][199][200][201][202][203][204] , had reductions of 1139-and 3207-fold in group A patients, respectively, and 3-and 32-fold in group B patients, respectively.…”