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 si ngle cytotoxic T lymphocyte (CTL) epitope from either the M2 protein o f respiratory syncytial virus (RSV) or from the nucleoprotein of measl es virus (MV) with or without a signal sequence (also called secretory or leader sequence). Following intradermal immunization, plasmids in which the CTL epitopes were expressed in-frame with the signal sequenc e were more effective at inducing peptide- and virus-specific CTL resp onses than plasmids expressing CTL epitopes without the signal sequenc e. This immunization resulted in protection against MV-induced encepha litis and a significant reduction in viral load following RSV challeng e. The reduction of viral load following RSV challenge was abrogated b y prior injection with anti-IFN-gamma antibodies. These results highli ght the ability of epitope-based DNA immunization to induce protective immune responses to well-defined epitopes and indicate the potential of this approach for the development of vaccines against infectious di seases.