SUBGROUP SPECIFIC PROTECTION OF MICE FROM RESPIRATORY SYNCYTIAL VIRUS-INFECTION WITH PEPTIDES ENCOMPASSING THE AMINO-ACID REGION-174-187 FROM THE G-GLYCOPROTEIN - THE ROLE OF CYSTEINYL RESIDUES IN PROTECTION

We identified subgroup specific protective epitopes represented by the amino acid regions 174-187 and 171-187 of the G glycoproteins from re spiratory syncytial virus (RSV), subgroups A and B. Mice immunized wit h coupled synthetic peptides corresponding to either the region 174-18 7 containing a Cys186-->Ser substitution or to the native region 171-1 87 were completely resistant to RSV infection but only to the respecti ve virus. The protective activities of the peptides 174-187 were depen dent on the Cys186-->Ser substitution, In addition, a recombinant prot ein representing the region 125-203 of the A subgroup G glycoprotein e xpressed in Escherichia coli was capable without further treatment to completely protect animals against RSV subgroup A infection. We show t hat the combinations of cysteinyl residues (positions 173, 176, 182, a nd 186) retained within either synthetic peptides or the recombinant p rotein G(125-203) greatly influenced their This indicates that the reg ion 171-187 is essential for the protection G(125-203) protein. Furthe rmore, our results strongly suggest that the peptides' and recombinant protein's potencies are a function of a loop-like structure which is stabilized by intramolecular disulfide linkages between Cys176-Cys182 and Cys173-Cys186. This is further supported by the observation that c hemical blocking of the sulfidryl groups in synthetic peptides complet ely eliminated their protective activity. (C) 1997 Elsevier Science Lt d.