Protective cytotoxic T lymphocyte responses against paramyxoviruses induced by epitope-based DNA vaccines: involvement of IFN-gamma

Plasmid DNA vectors have been constructed with minigenes encoding a singlecytotoxic T lymphocyte (CTL) epitope from either the M2 protein ofrespiratory syncytial virus (RSV) or from the nucleoprotein of measlesvirus (MV) with or without a signal sequence (also called secretory orleader sequence). Following intradermal immunization, plasmids in which theCTL epitopes were expressed in-frame with the signal sequence were moreeffective at inducing peptide- and virus- specific CTL responses thanplasmids expressing CTL epitopes without the signal sequence. Thisimmunization resulted in protection against MV-induced encephalitis and asignificant reduction in viral load following RSV challenge. The reductionof viral load following RSV challenge was abrogated by prior injection withanti-IFN-gamma antibodies. These results highlight the ability ofepitope-based DNA immunization to induce protective immune responses towell-defined epitopes and indicate the potential of this approach for thedevelopment of vaccines against infectious diseases.