Long-lasting anti-viral cytotoxic T lymphocytes induced in vivo with chimeric-multirestricted lipopeptides

• Published in: Vaccine Vol. 13; no. 14; pp. 1339 - 1345
• Main Authors: Sauzet, Jean-Pierre, Déprez, Benoit, Martinon, Frédéric, Guillet, Jean-Gérard, Gras-Masse, Hélène, Gomard, Elisabeth
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 1995; Elsevier
• Subjects: AIDS/HIV; Animals; Biological and medical sciences; CD8-Positive T-Lymphocytes - immunology; Chick Embryo; Cytotoxic T lymphocytes; Epitopes - immunology; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Haplotypes; human immunodeficiency virus 1; Immunobiology; Influenza A virus - immunology; Influenza B virus - immunology; Influenza Vaccines - pharmacology; lipopeptide; Lipoproteins - immunology; Lipoproteins - pharmacology; long-lasting responses; Mice; Mice, Inbred Strains; Modulation of the immune response (stimulation, suppression); Nucleoproteins - immunology; Recombinant Fusion Proteins - immunology; Recombinant Fusion Proteins - pharmacology; Sensitivity and Specificity; T-Lymphocytes, Cytotoxic - drug effects; T-Lymphocytes, Cytotoxic - immunology; T-Lymphocytes, Helper-Inducer - drug effects; T-Lymphocytes, Helper-Inducer - immunology; Time Factors; Viral Proteins - immunology; lipopeptide; long-lasting responses; Cytotoxic T lymphocytes; Immunostimulation; Immune response; Antigenic determinant; Rodentia; Orthomyxoviridae; Cytotoxicity; Cellular immunity; Vaccine; Lipoprotein; Influenzavirus; Virus; Vertebrata; Mammalia; Synthetic product; Mouse; T-Lymphocyte; Chimera
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/0264-410X(94)00087-4

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.