Division of Collaboration and Education, Hokkaido University Research Center for Zoonosis Control, Sapporo, Japan.
PLoS One. 2013;8(3):e60068. doi: 10.1371/journal.pone.0060068. Epub 2013 Mar 22.
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.
为了通过基于肽的疫苗诱导有效的表位特异性 T 细胞免疫，表位肽必须在体内有效地递送到抗原呈递细胞 (APC)。因此，选择合适的肽载体对于开发有效的肽疫苗至关重要。在这项研究中，我们探索了新的肽载体，这些载体在细胞毒性 T 淋巴细胞 (CTL)诱导能力方面显示出增强作用。
方法/主要发现：来自表位特异性体内 CTL 测定的数据表明，磷脂酰丝氨酸 (PS) 在测试的候选材料中具有很强的佐剂作用。进一步的分析表明，与多脂质体缀合物或未缀合的抗原相比，PS 缀合的抗原优先且有效地被专业 APC 捕获，特别是 CD11c(+)CD11b(+)MHCII(+) 常规树突状细胞 (cDC)。此外，PS 证明了体内肽特异性辅助 T 细胞的刺激能力。
结论/意义：这项工作表明 PS 是一种易于制备的高效载体，具有简单的结构，可有效地将抗原递送到专业 APC，并在体内诱导辅助和细胞毒性 T 细胞反应。因此，PS 是一种有前途的新型 T 细胞诱导肽疫苗佐剂。
