CTL epitopes identified with a defective recombinant adenovirus expressingmeasles virus nucleoprotein and evaluation of their protective capacity inmice

Cytotoxic T-lymphocyte (CTL) responses to measles virus (MV) play an import ant role in recovery from infection, with one of the major target proteins for CTL activity being the nucleoprotein (Np). In this report, a replicatio n-deficient adenovirus-5 recombinant, expressing for MV Np (Rad68) was test ed for in vivo priming of MV Np-specific CTL responses in BALB/c and CBA mi ce. In both strains of mice strong Np-specific CTL responses were induced a nd these responses were shown to be MHC class I restricted. Using overlappi ng 15mer peptides spanning residues 1-505 of MV Np a single epitope compris ing residues 281-295 was identified in BALB/c mice whereas, in CBA mice two epitopes comprising residues 51-65 and 81-95, were identified. These epito pes were found to contain class I motifs for H-2L(d) and H-2K(k) MHC molecu les, respectively. Immunization of BALB/c and CBA mice with the respective CTL epitopes resulted in the in vivo induction of peptide-and MV Np-specifi c CTL responses. In addition, the identified H-2Kk restricted CTL epitopes conferred some protection against encephalitis induced following intracereb ral challenge with a lethal dose of canine distemper virus (the Np of which shares 70% sequence homology with MV Np). These findings highlight the pot ential of using well-defined CTL epitopes to control virus infection. (C) 1 999 Elsevier Science B.V. All rights reserved.