Translating innate response into long-lasting antibody response by the intrinsic antigen-adjuvant properties of papaya mosaic virus
Translating innate response into long-lasting antibody response by the intrinsic antigen-adjuvant properties of papaya mosaic virus
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DOI：
10.1111/j.1365-2567.2007.02753.x
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发表时间：
2008-06-01
期刊：
影响因子：
6.4
通讯作者：
Lopez-Macias, Constantino
中科院分区：
文献类型：
--
作者：
Acosta-Ramirez, Elizabeth;Perez-Flores, Rebeca;Lopez-Macias, Constantino
识别参与有效激活先天性和适应性免疫应答的分子的特性，从而导致持久的免疫力，这对于疫苗和佐剂的开发至关重要。在这里，我们表明，木瓜花叶病毒（PapMV）被识别的免疫系统作为病原体相关的分子模式（PAMP）和作为抗原在小鼠（Pamptigen）。没有添加佐剂的PapMV的单次免疫有效地诱导细胞和特异性持久抗体应答。PapMV还有效地激活先天免疫应答，如通过诱导脂筏聚集、分泌促炎细胞因子、上调树突状细胞和巨噬细胞上的共刺激分子以及对模型抗原的特异性抗体应答的持久佐剂作用所示。PapMV与伤寒沙门氏菌混合。伤寒沙门氏菌外膜蛋白C对伤寒沙门氏菌攻击的保护作用增强。伤寒杆菌，揭示了PapMV在诱导免疫中的内在佐剂特性。负载有PapMV的抗原呈递细胞在体内有效地诱导抗体应答，这可能将观察到的先天性和适应性应答联系起来。PapMV作为Pamptigen的识别可能会转化为持久的抗体应答和保护作用。这些特性可用于开发新的疫苗平台。
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.