Abstract
BackgroundTo 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 FindingsData 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/SignificanceThis 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.
Highlights
The immune system generates antibody-based humoral and T cell-based cellular immune responses to viruses, bacteria, and protozoa by recognizing a variety of components of the pathogen
In vivo cytotoxicity assay data showed that NP366–374 (A/ HK483) peptide conjugated with chitosan, dendrimer, or carboxymethyl cellulose (CMC) did not induce epitope-specific cytotoxic T lymphocyte (CTL) at all, which was less than unconjugated peptide alone
Enhancement of the CTL induction effect by PS was confirmed by NP366–374 from another influenza virus strain (A/PR8) or OVA257–264 (Figure 2A)
Summary
The immune system generates antibody-based humoral and T cell-based cellular immune responses to viruses, bacteria, and protozoa by recognizing a variety of components of the pathogen. Synthetic peptides have been shown to be a practical and useful vaccine since they are minimized T cell epitopes and would not be expected to induce harmful side effects. They can be produced [2], synthesized artificially, stored lyophilized at room temperature, and can be modified with functional chemical compounds. The antigenicity of the peptide was significantly improved by liposome conjugation and induced potent specific CTL responses in vivo, which led to protection from lethal influenza virus infection in mice [4,5]. We explored new peptide carriers which show enhancement in cytotoxic T lymphocyte (CTL) induction capability
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