PROTECTION AGAINST MORBILLIVIRUS-INDUCED ENCEPHALITIS BY IMMUNIZATIONWITH A RATIONALLY DESIGNED SYNTHETIC PEPTIDE VACCINE CONTAINING B-CELL AND T-CELL EPITOPES FROM THE FUSION PROTEIN OF MEASLES-VIRUS

Synthetic peptides representing T- and B-cell epitopes from the fusion (F) protein of measles virus (MV) were tested for their ability to in duce a protective immune response against intracerebral challenge with neuroadapted strains of MV and canine distemper virus (CDV) in mice. Of the panel of peptides tested, only a chimeric peptide consisting of two copies of a promiscuous T-cell epitope (representing residues 288 to 302 of MV F protein) synthesized at the amino terminus of a B-cell epitope (representing residues 404 to 414 of MV F protein) was able t o induce a protective response against challenge with MV and CDV in in bred mice. The protective response induced by this peptide (TTB) was a ssociated with a significant reduction in mortality, histological abse nce of acute encephalitis, and greatly reduced titers of virus in the brains of TTB-immune mice following challenge compared with the result s for nonimmunized controls. A chimeric peptide comprising one copy of the T-cell epitope and one copy of the B-cell epitope (TB) did not in duce a protective response. A comparison of the antibody responses ind uced by the two chimeras suggested that differences in protective effi cacy following immunization may be a result of the higher affinity of the antibody induced by the TTB peptide than that of the antibody indu ced by the TB peptide. In addition, differences in the immunoglobulin G subclass of the antipeptide antibody responses were observed, and th ese may play a role in the differences in protection observed. These r esults indicate that appropriately designed synthetic peptides have po tential as vaccines for the induction of cross-reactive protection aga inst morbilliviruses.