Nasal Immunization with a Fusion Protein Consisting of the Hemagglutinin A Antigenic Region and the Maltose-Binding Protein Elicits CD11c+ CD8+ Dendritic Cells for Induced Long-Term Protective Immunity
Nasal Immunization with a Fusion Protein Consisting of the Hemagglutinin A Antigenic Region and the Maltose-Binding Protein Elicits CD11c+ CD8+ Dendritic Cells for Induced Long-Term Protective Immunity
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DOI：
10.1128/iai.01203-10
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发表时间：
2011-02-01
影响因子：
3.1
通讯作者：
Yamamoto, Masafumi
中科院分区：
文献类型：
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作者：
Du, Yuan;Hashizume, Tomomi;Yamamoto, Masafumi
我们评估了由牙龈卟啉单胞菌血凝素A的25 kDa抗原区域和大肠杆菌麦芽糖结合蛋白（25 k-hagA-MBP）组成的融合蛋白作为预防牙龈卟啉单胞菌口腔感染的鼻用疫苗的功效。用25 k-hagA-MBP进行鼻免疫以Toll样受体4（TLR 4）依赖的方式诱导高水平的25 k-hagA特异性血清IgG、血清伊加和唾液伊加抗体。这些抗体反应在免疫后至少维持1年。细胞因子应答分析显示，鼻腔给药25 k-hagA-MBP可诱导脾和颈淋巴结（CLN）中抗原特异性CD 4（+）T细胞产生白细胞介素4（IL-4）和IL-5，但不产生γ干扰素（IFN-γ）。此外，在脾脏、CLN和鼻咽相关淋巴网状组织（NALT）中观察到CD 11 c（+）CD 8 α（+）数量增加，但CD 11 c（+）CD 11b（+）或CD 11 c（+）B220（+）、树突状细胞（CD 80、CD 86、CD 40和主要组织相容性复合物II类（MHC II）分子表达上调）数量增加。有趣的是，当鼻内给予25 k-hagA-MBP或霍乱毒素（CT）以检查它们在神经元组织中的存在时，25 k-hagA-MBP的量显著低于CT的量。重要的是，经鼻给予25 k-hagA-MBP的小鼠显示出由牙龈卟啉单胞菌口腔感染引起的牙槽骨损失的显著减少，甚至在免疫后1年。这些结果表明，25 k-hagA-MBP鼻腔给药将是一种有效和安全的粘膜疫苗对牙龈卟啉单胞菌感染，并可能是一个重要的工具，预防慢性牙周炎在人类。
We assessed the efficacy of a fusion protein consisting of the 25-kDa antigenic region of Porphyromonas gingivalis hemagglutinin A and the Escherichia coli maltose-binding protein (25k-hagA-MBP) as a nasal vaccine for the prevention of oral infection with P. gingivalis. Nasal immunization with 25k-hagA-MBP induced high levels of 25k-hagA-specific serum IgG, serum IgA, and salivary IgA antibodies in a Toll-like receptor 4 (TLR4)-dependent manner. These antibody responses were maintained for at least 1 year after immunization. Analysis of cytokine responses showed that nasal administration of 25k-hagA-MBP induced antigen-specific CD4(+) T cells producing interleukin 4 (IL-4) and IL-5, but not gamma interferon (IFN-gamma), in the spleen and cervical lymph nodes (CLNs). Furthermore, increased numbers of CD11c(+) CD8 alpha(+), but not CD11c(+) CD11b(+) or CD11c(+) B220(+), dendritic cells with upregulated expression of CD80, CD86, CD40, and major histocompatibility complex class II (MHC II) molecules were noted in the spleen, CLNs, and nasopharynx-associated lymphoreticular tissues (NALT). Interestingly, when 25k-hagA-MBP or cholera toxin (CT) was given intranasally to enable examination of their presence in neuronal tissues, the amounts of 25k-hagA-MBP were significantly lower than those of CT. Importantly, mice given 25k-hagA-MBP nasally showed a significant reduction in alveolar bone loss caused by oral infection with P. gingivalis, even 1 year after the immunization. These results suggest that 25k-hagA-MBP administered nasally would be an effective and safe mucosal vaccine against P. gingivalis infection and may be an important tool for the prevention of chronic periodontitis in humans.