Emulsified phosphatidylserine, simple and effective peptide carrier for induction of potent epitope-specific T cell responses

PLoS One. 2013;8(3):e60068. doi: 10.1371/journal.pone.0060068. Epub 2013 Mar 22.

Abstract

Background: To induce potent epitope-specific T cell immunity by a peptide-based vaccine, epitope peptides must be delivered efficiently to antigen-presenting cells (APCs) in vivo. Therefore, selecting an appropriate peptide carrier is crucial for the development of an effective peptide vaccine. In this study, we explored new peptide carriers which show enhancement in cytotoxic T lymphocyte (CTL) induction capability.

Methodology/principal findings: Data from an epitope-specific in vivo CTL assay revealed that phosphatidylserine (PS) has a potent adjuvant effect among candidate materials tested. Further analyses showed that PS-conjugated antigens were preferentially and efficiently captured by professional APCs, in particular, by CD11c(+)CD11b(+)MHCII(+) conventional dendritic cells (cDCs) compared to multilamellar liposome-conjugates or unconjugated antigens. In addition, PS demonstrated the stimulatory capacity of peptide-specific helper T cells in vivo.

Conclusions/significance: This work indicates that PS is the easily preparable efficient carrier with a simple structure that delivers antigen to professional APCs effectively and induce both helper and cytotoxic T cell responses in vivo. Therefore, PS is a promising novel adjuvant for T cell-inducing peptide vaccines.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigen-Presenting Cells / immunology
  • Antigen-Presenting Cells / metabolism*
  • CD11b Antigen / metabolism
  • CD11c Antigen / metabolism
  • CD4-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / metabolism
  • Cells, Cultured
  • Dendritic Cells / immunology
  • Epitopes / immunology*
  • Epitopes, T-Lymphocyte / immunology*
  • Mice
  • Phosphatidylserines / chemistry*
  • T-Lymphocytes, Cytotoxic / immunology

Substances

  • CD11b Antigen
  • CD11c Antigen
  • Epitopes
  • Epitopes, T-Lymphocyte
  • Phosphatidylserines

Grants and funding

Financial support for this study was supported by the grant from the Ministry of Education, Culture, Sports, Science and Technology (MEXT), Japan, for Joint Research Program of the Research Center for Zoonosis Control, Hokkaido University and also by the Japan Initiative for Global Research Network on Infections Diseases (J-GRID) programmed by the MEXT, Japan (http://www.crnid.riken.jp/jgrid/en/index.html). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.