中文摘要：研究表明，全灭活流感病毒可作为流感肽抗原的佐剂，将流感-M1 GILGFVFTL肽（GIL）与全灭活流感病毒（WIV）联合免疫HLA-A2.1转基因小鼠，能够诱导小鼠产生肽特异性CD8(+)T细胞，无论GIL还是WIV均对GIL-特异性T细胞反应起作用。然而，将肽抗原与WIV进行共定位非常重要，肽和WIV即不进行物理性融合，WIV的膜融合活性与WIV的佐剂作用也不相关。研究进一步表明，WIV可以作为佐剂诱导针对一系列肽的T细胞反应。该研究揭示了WTV作为流感肽佐剂的应用潜力。WIV具有生产简单、安全性稳定等优点，因此WIV是T细胞肽的一种有效佐剂，可应用于非流感抗原的免疫。
外文摘要： Influenza peptide antigens coding for conserved T cell epitopes have the capacity to induce cross-protective influenza-specific immunity. Short peptide antigens used as a vaccine, however, often show poor immunogenicity. In this study, we demonstrate that whole-inactivated influenza virus (WIV) acts as an adjuvant for influenza peptide antigens, as shown by the induction of peptide-specific CD8(+) T cells in HLA-A2.1 transgenic mice upon vaccination with the influenza-M1-derived GILGFVFTL peptide (GIL), formulated with WIV. By screening various concentrations of GIL and WIV, we found that both components contributed to the GIL-specific T cell response. Whereas co-localization of the peptide antigen and WIV adjuvant was found to be important, neither physical association between peptide and WIV nor fusogenic activity of WIV were relevant for the adjuvant effect of WIV. We furthermore show that WIV may adjuvate T cell responses to a variety of peptides, using pools of either conserved wild-type influenza peptides or chemically altered peptide ligands. This study shows the potential of WIV as an adjuvant for influenza peptides. The simple formulation process and the solid safety record of WIV make this an attractive adjuvant for T cell peptides, and may also be used for non-influenza antigens.
外文关键词：whole-inactivated influenza virus, adjuvant, T cell peptide, CTL, design of experiments, formulation, peptide vaccine
作者：Soema, PC; Huber, SKR; Willems, GJ; Jacobi, R; Hendriks, M; Soethout, E; Jiskoot, W; de Jonge, J; van Beek, J; Kersten, GFA; Amorij, JP
作者单位：新西兰 Intravacc Inst Translat Vaccinol
期刊名称：FRONTIERS IN IMMUNOLOGY
期刊影响因子：6.43
出版年份：2018
出版刊次：3
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