Linkage of a fusion peptide to a CTL epitope from the nucleoprotein of measles virus enables incorporation into ISCOMs and induction of CTL responses following intranasal immunization.
The introduction of soluble protein antigens into the endogenous processing pathway is a prerequisite for the efficient induction of MHC class-1 restricted cytotoxic T-lymphocytes (CTLs). Antigens incorporated into immunostimulating complexes (ISCOMs) containing lipids and Quil-A are able to induce CD8+ CTL responses in vivo. Furthermore, lipopeptides have also been used to raise peptide-specific CTLs and bypass the requirement for the use of an adjuvant. Although conventional ISCOM technology is in general restricted to the use of hydrophobic proteins or fatty acid-derivitized proteins or peptides, we have demonstrated that the linkage of a conserved paramyxovirus fusion peptide to a CTL epitope NP29 (residues 281-290 of measles virus nucleoprotein) resulted in the incorporation of this hydrophilic CTL epitope into ISCOMs and the in vivo priming of peptide specific CTLs following intranasal immunization. In addition, the fusion peptide-CTL epitope chimera was able to efficiently sensitise P815 target cells for lysis by nucleoprotein specific CTLs induced following immunization of mice with recombinant RAd-68 adenovirus, suggesting the efficient introduction of the peptide into the class-1 restricted antigen processing pathway. Furthermore, immunization of mice with this fusion peptide chimera in saline was able to prime an NP29-specific CTL response despite the absence of adjuvant.
Department of Clinical Sciences, London School of Hygiene and Tropical Medicine, UK.
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SC
Hsu
E B
EB
Schadeck
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A
Delmas
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M
Shaw
M W
MW
Steward
D016475:3T3 Cells; D000256:Adenoviridae / Q000235:genetics; D000281:Administration, Intranasal; D000818:Animals; D005620:Freund's Adjuvant; D016882:ISCOMs; D051379:Mice; D008807:Mice, Inbred BALB C; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000276:immunology; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014764:Viral Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*
D016882:ISCOMs; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins; D011993:Recombinant Fusion Proteins; D014764:Viral Proteins; C058314:nucleoprotein, Measles virus; D005620:Freund's Adjuvant