Del Prete G, Santi L, Andrianaivoarimanana V, Amedei A, Domarle O, D' Elios M M, Arntzen C J, Rahalison L, Mason H S
Department of Internal Medicine, University of Florence and Department of Biomedicine, Azienda Ospedaliera Universitaria Careggi, Florence, Italy.
Int J Immunopathol Pharmacol. 2009 Jan-Mar;22(1):133-43. doi: 10.1177/039463200902200115.
Plague is still endemic in different regions of the world. Current vaccines raise concern for their side effects and limited protection, highlighting the need for an efficacious and rapidly producible vaccine. F1 and V antigens of Yersinia pestis, and F1-V fusion protein produced in Nicotiana benthamiana administered to guinea pigs resulted in immunity and protection against an aerosol challenge of virulent Y. pestis. We examined the effects of plant-derived F1, V, and F1-V on human cells of the innate immunity. F1, V, and F1-V proteins engaged TLR2 signalling and activated IL-6 and CXCL-8 production by monocytes, without affecting the expression of TNF-alpha, IL-12, IL-10, IL-1beta, and CXCL10. Native F1 antigen and recombinant plant-derived F1 (rF1) and rF1-V all induced similar specific T-cell responses, as shown by their recognition by T-cells from subjects who recovered from Y. pestis infection. Native F1 and rF1 were equally well recognized by serum antibodies of Y. pestis-primed donors, whereas serological reactivity to rF1-V hybrid was lower, and that to rV was virtually absent. In conclusion, plant-derived F1, V, and F1-V antigens are weakly reactogenic for human monocytes and elicit cell-mediated and humoral responses similar to those raised by Y. pestis infection.
鼠疫在世界不同地区仍然流行。目前的疫苗因其副作用和保护作用有限而令人担忧，这凸显了对一种有效且能快速生产的疫苗的需求。将烟草中产生的鼠疫耶尔森菌的F1和V抗原以及F1-V融合蛋白接种给豚鼠，可使其产生免疫力并抵御强毒性鼠疫耶尔森菌的气溶胶攻击。我们研究了植物源F1、V和F1-V对先天免疫的人类细胞的影响。F1、V和F1-V蛋白参与Toll样受体2（TLR2）信号传导，并激活单核细胞产生白细胞介素-6（IL-6）和CXC趋化因子配体8（CXCL-8），而不影响肿瘤坏死因子-α（TNF-α）、白细胞介素-12（IL-12）、白细胞介素-10（IL-10）、白细胞介素-1β（IL-1β）和CXC趋化因子配体10（CXCL10）的表达。天然F1抗原以及重组植物源F1（rF1）和rF1-V均诱导了相似的特异性T细胞反应，从鼠疫耶尔森菌感染中康复的受试者的T细胞对它们的识别即表明了这一点。鼠疫耶尔森菌致敏供体的血清抗体对天然F1和rF1的识别程度相同，而对rF1-V杂交体的血清学反应性较低，对rV几乎没有反应。总之，植物源F1、V和F1-V抗原对人类单核细胞的反应原性较弱，并引发与鼠疫耶尔森菌感染所引发的相似的细胞介导和体液反应。
