In vivo priming of virus-specific cytotoxic T lymphocytes with synthetic lipopeptide vaccine

Abstract

Cytotoxic T lymphocytes (CTL) constitute an essential part of the immune response against viral infections. Such CTL recognize peptides derived from viral proteins together with major histocompatibility complex (MHC) class I molecules on the surface of infected cells, and usually require in vivo priming with infectious virus. Here we report that synthetic viral peptides covalently linked to tripalmitoyl-S-glycerylcysteinyl-seryl-serine (P3CSS) can efficiently prime influenza-virus-specific CTL in vivo. These lipopeptides are able to induce the same high-affinity CTL as does the infectious virus. Our data are not only relevant to vaccine development, but also have a bearing on basic immune processes leading to the transition of virgin T cells to activated effector cells in vivo, and to antigen presentation by MHC class I molecules.

The Dual Role of Lipids of the Lipoproteins in Trumenba, a Self-Adjuvanting Vaccine Against Meningococcal Meningitis B Disease

“…It was discovered in the late 1980s that conjugation of Pam3CSS (tripalmitoyl Cys-SerSer) or Pam2CSS (di-O-acylated palmitoyl Cys-Ser-Ser) to peptides derived from bacterial or viral proteins could convert the immunologically inactive peptides into potent vaccines that provided long-lasting protection against bacterial or viral infections in animal models. This effect was enabled by induction of neutralizing antibodies (28,29) and by in vivo priming of epitope-specific cytotoxic T cells and memory T cells (30)(31)(32). Since antibodies to the lipid moieties are not generated in vivo, the immune-enhancing effect of the lipids is believed to be similar to that of a conventional adjuvant, and thus, bacterial lipoprotein/lipopeptidecontaining vaccines are recognized as one category of selfadjuvanting vaccines (21)(22)(23)33).…”

Cellular Immune Recognition and the Biological Role of Major Transplantation Antigens

“…The recognition that peptides derived from viruses, bacteria, or classical parasites are presented to T-cells via MHC class I or class II molecules immediately suggested that instead of live, and therefore potentially harmful, infectious agents, peptides could possibly be used as vaccines to induce T-cell responses [80]. This was first formally shown for virus-specific peptides in studies by M. Schultz, P. Aichele, and H. Hengartner [81] ( Table 2, Fig.…”

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)

“…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.…”