A synthetic peptide that contains a Semliki Forest virus (SFV) B cell epitope, located at amino acid positions 240 to 255 of the E2 protein, and an SFV T helper (T) cell epitope, located at positions 137 to 151 of the E2 protein, evoked high titres of SFV-reactive antibodies in H-2 mice. Although the peptide-induced antibodies did not neutralize SFV , 70 to 100% of the peptide-immunized mice were protected against SFV, even when viral challenge was presented 4 months after immunization. The protection could be transferred by anti-peptide serum, indicating that antibodies were responsible for the protection. When the T cell epitope of this protective peptide was replaced by an influenza virus T cell epitope or by another SFV T cell epitope, the resulting peptides induced lower non-neutralizing SFV-reactive antibody titres and protected a correspondingly lower percentage of mice (50% and 30%, respectively). A peptide with the same T cell epitope as the best protective peptide but with a less effective SFV B cell epitope protected only 33% of the mice. These results indicate that protection against SFV by a synthetic peptide is primarily dependent on its ability to induce adequate amounts of antibodies with relevant specificity and sufficient affinity; the ability to induce a relevant (SFV-specific) T memory response played only a minor role in protection.


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