Long-lasting anti-viral cytotoxic T lymphocytes induced in vivo with chimeric-multirestricted lipopeptides.
Cytotoxic T lymphocytes (CTL) play a major role in protective immunity against viral diseases. However, the antigenic formulations that can be used in vaccinations able to generate virus-specific CTL responses in vivo have yet to be defined. We have previously shown that HIV-1-specific CTL can be elicited in mice by injecting without adjuvant a synthetic peptide of the envelope glycoprotein that has been modified by the addition of a simple lipid tail to the end of the sequence (lipopeptide). The present study set out to address the question of whether such immunogens may be appropriate for preparing a human synthetic vaccine. We first showed that CTL were effectively induced by lipopeptides when given s.c. or i.p. We evidenced that the in vivo induction required stimulation of a concomitant specific T helper cell response, implying the presence of at least one CD4 epitope in the synthetic sequence used. Bearing in mind the particular properties that would be required in a prospective human peptide vaccine, we conceived a strategy in which a virus-specific CTL response could be generated in mice of different haplotypes using a single lipopeptide. We therefore tested a lipopeptide construct that integrated a synthetic sequence having three colinear epitopes of the influenza virus nucleoprotein, each restricted to a different H-2 haplotype. We found that a CTL response could be elicited to all three epitopes of this chimeric multirestricted lipopeptide construct. Finally, we have attempted to estimate the duration of the responses; strong CTL activities were still present up to six months after the last injection. These findings indicate that this approach may be suitable for developing a synthetic vaccine for human use.
Sauzet
J P
JP
Laboratoire d'Immunologie des Intéractions Cellulaires et Moléculaires, INSERM U152, Institut Cochin de Génétique Moléculaire, Paris, France.
Déprez
B
B
Martinon
F
F
Guillet
J G
JG
Gras-Masse
H
H
Gomard
E
E
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002642:Chick Embryo; D000939:Epitopes / Q000276:immunology; D006239:Haplotypes; D009980:Influenza A virus / Q000276:immunology; D009981:Influenza B virus / Q000276:immunology*; D007252:Influenza Vaccines / Q000494:pharmacology; D008074:Lipoproteins / Q000276:immunology* / Q000494:pharmacology*; D051379:Mice; D008815:Mice, Inbred Strains; D009698:Nucleoproteins / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000276:immunology* / Q000494:pharmacology*; D012680:Sensitivity and Specificity; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects / Q000276:immunology; D013997:Time Factors; D014764:Viral Proteins / Q000276:immunology
D000939:Epitopes; D007252:Influenza Vaccines; D008074:Lipoproteins; D009698:Nucleoproteins; D011993:Recombinant Fusion Proteins; D014764:Viral Proteins