Development of a lipopeptide-based therapeutic vaccine to treat chronic HBV infection. I. Induction of a primary cytotoxic T lymphocyte response in humans.

Abstract

Our goal is to use peptide epitopes that are recognized by cytotoxic T lymphocytes (CTL) carried out in 26 normal subjects showed that the vaccine was safe and able to induce a primary HBV-specific CTL response. A dose-response curve was observed and five out of five subjects responded to the 500-jig dose. (J. Clin. Invest. 1995. 95:341-349.)

Peptide immunization in humans: a combined CD8+/CD4+ T cell-targeted vaccine restimulates the memory CD4 T cell response but fails to induce cytotoxic T lymphocytes (CTL)

“…This indicates that the assays used were suitable to detect CTL directed against one certain epitope and at frequencies encountered in a non-persisting infection like influenza. Together with a recent report by Vitiello et al [18] and the fact that the volunteers were boosted twice, this suggests that the assays used here should have been sensitive enough to monitor a successful CTL induction.…”

“…As seen with the flu peptide, the precursor frequencies against one common epitope are low and vary widely between individuals and over time in the same individual [31,36]. As Vitiello et al have shown, successful CTL induction can lead to strong cytotoxic responses [18]. Thus, although we can not rule out that a moderate HIV peptide-specific cytotoxicity was generated, we consider our results negative.…”

“…To achieve that, it could be advantageous to chemically link the T helper epitope and the CTL peptide [16,18,35]. Such linkage would also contribute to the stability of the two peptides, but may have the drawback that it could lead to the generation of antibodies and the formation of new CTL epitopes.…”

“…Furthermore, attachment of a lipophilic tail to the conjugate may improve the uptake and appropriate processing. On the other hand, the use of lipophilic compounds may complicate the manufacturing and purification of the vaccine [18,20]. Indeed, a most recent study in mice indicates that both the linkage of the two T cell epitopes and the modification with a lipo-tail (lipopeptides) strongly enhanced the immunogenicity of a peptidebased vaccine.…”

“…Indeed, several animal studies showed that immunization with short, MHC class I-binding peptides was successfully inducing a CTL response in vivo which can protect from persistent infection. Furthermore, it was shown that the simultaneous injection of a MHC class II-restricted T helper epitope and a MHC class I-binding CTL epitope strongly enhanced the generation of peptide-specific CTL, compared with injection of the CTL peptide alone [9,[14][15][16][17][18][19][20]. The beneficial effect of this co-administration is thought to be due to the induction of CD4 T cell help supporting the generation of CD8 CTL.…”