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Translating innate response into long-lasting antibody response by the intrinsic antigen-adjuvant properties of papaya mosaic virus

机译:通过木瓜花叶病毒的内在抗原佐剂特性将先天应答转化为持久抗体应答

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摘要

Identifying the properties of a molecule involved in the efficient activation of the innate and adaptive immune responses that lead to long-lasting immunity is crucial for vaccine and adjuvant development. Here we show that the papaya mosaic virus (PapMV) is recognized by the immune system as a pathogen-associated molecular pattern (PAMP) and as an antigen in mice (Pamptigen). A single immunization of PapMV without added adjuvant efficiently induced both cellular and specific long-lasting antibody responses. PapMV also efficiently activated innate immune responses, as shown by the induction of lipid raft aggregation, secretion of pro-inflammatory cytokines, up-regulation of co-stimulatory molecules on dendritic cells and macrophages, and long-lasting adjuvant effects upon the specific antibody responses to model antigens. PapMV mixed with Salmonella enterica serovar Typhi (S. typhi) outer membrane protein C increased its protective capacity against challenge with S. typhi, revealing the intrinsic adjuvant properties of PapMV in the induction of immunity. Antigen-presenting cells loaded with PapMV efficiently induced antibody responses in vivo, which may link the innate and adaptive responses observed. PapMV recognition as a Pamptigen might be translated into long-lasting antibody responses and protection observed. These properties could be used in the development of new vaccine platforms.
机译:鉴定与先天性和适应性免疫反应的有效激活有关的分子的特性,这种免疫反应可导致持久的免疫力,对于疫苗和佐剂的开发至关重要。在这里,我们显示木瓜花叶病毒(PapMV)被免疫系统识别为病原体相关分子模式(PAMP)和小鼠中的抗原(Pamptigen)。不添加佐剂的单次PapMV免疫有效诱导细胞和特异性持久抗体应答。 PapMV还可以有效激活先天性免疫反应,如脂质筏聚集的诱导,促炎性细胞因子的分泌,树突状细胞和巨噬细胞上共刺激分子的上调以及对特定抗体反应的长期佐剂作用所示模拟抗原。 PapMV与肠炎沙门氏菌伤寒沙门氏菌(S. typhi)外膜蛋白C混合,提高了其对伤寒沙门氏菌攻击的保护能力,揭示了PapMV在诱导免疫中的内在佐剂特性。载有PapMV的抗原提呈细胞可在体内有效诱导抗体反应,这可能与观察到的先天反应和适应性反应联系在一起。将PapMV识别为Pamptigen可能会转化为持久的抗体反应并观察到保护作用。这些特性可用于开发新的疫苗平台。

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