Document 0802
 DOCN  M9650802
 TI    Long-lasting anti-viral cytotoxic T lymphocytes induced in vivo with
       chimeric-multirestricted lipopeptides.
 DT    9605
 AU    Sauzet JP; Deprez B; Martinon F; Guillet JG; Gras-Masse H; Gomard E;
       Laboratoire d'Immunologie des Interactions Cellulaires et; Moleculaires,
       INSERM U152, Institut Cochin de Genetique; Moleculaire, Paris, France.
 SO    Vaccine. 1995 Oct;13(14):1339-45. Unique Identifier : AIDSLINE
       MED/96155144
 AB    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.
 DE    Animal  Chick Embryo  Chimeric Proteins/*IMMUNOLOGY/*PHARMACOLOGY
       CD8-Positive T-Lymphocytes/IMMUNOLOGY  Epitopes/IMMUNOLOGY  Haplotypes
       Influenza Vaccine/PHARMACOLOGY  Lipoproteins/*IMMUNOLOGY/*PHARMACOLOGY
       Mice  Mice, Inbred Strains  Nucleoproteins/IMMUNOLOGY  Orthomyxovirus
       Type A, Human/IMMUNOLOGY  Orthomyxoviruses Type B/*IMMUNOLOGY
       Sensitivity and Specificity  T-Lymphocytes, Cytotoxic/DRUG
       EFFECTS/*IMMUNOLOGY  T-Lymphocytes, Helper-Inducer/DRUG
       EFFECTS/IMMUNOLOGY  Time Factors  Viral Proteins/IMMUNOLOGY  JOURNAL
       ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).