Shim Doo-Hee, Chang Sun-Young, Park Sung-Moo, Jang Hyun, Carbis Rodney, Czerkinsky Cecil, Uematsu Satoshi, Akira Shizuo, Kweon Mi-Na
Mucosal Immunology Section, International Vaccine Institute, Seoul National University Research Park, Kwanak-Gu, Seoul 151-818, Republic of Korea.
Vaccine. 2007 Jun 15;25(25):4828-36. doi: 10.1016/j.vaccine.2007.03.050. Epub 2007 Apr 20.
Shigellosis is a major form of bacillary dysentery caused by Shigella infection. Shigella ribosome-based vaccines (SRV), considered among the potent vaccine candidates, are composed of O-antigen and ribosome isolated from S. flexneri 2a. To investigate the immunogenicity and protective efficacy of SRV, mice were vaccinated with SRV via the intranasal (i.n.) route. Interestingly, robust levels of Shigella-derived LPS-specific IgG and IgA Abs and antibody-forming cells were elicited in systemic and mucosal compartments following two i.n. administrations of SRV. Groups of mice receiving i.n. SRV developed milder pulmonary pneumonia upon challenge with virulent S. flexneri 2a than did those receiving parenteral SRV. We further found that the MyD88-dependent TLR2 signal partially mediates SRV-induced mucosal immunity, with the exception of TLR4- and TLR5-governed innate immunity. Most importantly, polymeric immunoglobulin receptor knockout (pIgR-/-) mice, which lack secretory IgA Ab, were afforded less protective efficacy than were wild-type mice. It can be concluded then that SRV is immunogenic and provides protective efficacy in mice. It can also be surmised that a mucosal SRV vaccine would be particularly relevant in targeting shigellosis, which provokes inflammation in the human colon.
志贺氏菌病是由志贺氏菌感染引起的细菌性痢疾的主要形式。基于志贺氏菌核糖体的疫苗（SRV）被认为是有效的候选疫苗之一，它由从福氏志贺氏菌2a分离的O抗原和核糖体组成。为了研究SRV的免疫原性和保护效果，通过鼻内（i.n.）途径给小鼠接种SRV。有趣的是，在两次鼻内接种SRV后，全身和黏膜部位均诱导出了高水平的志贺氏菌来源的LPS特异性IgG和IgA抗体以及抗体形成细胞。与接受肠胃外SRV的小鼠相比，接受鼻内SRV的小鼠组在用强毒性福氏志贺氏菌2a攻击后发生的肺炎症状较轻。我们进一步发现，除了由TLR4和TLR5调控的固有免疫外，依赖MyD88的TLR2信号部分介导了SRV诱导的黏膜免疫。最重要的是，缺乏分泌型IgA抗体的多聚免疫球蛋白受体敲除（pIgR-/-）小鼠所获得的保护效果不如野生型小鼠。因此可以得出结论，SRV具有免疫原性，并在小鼠中提供保护效果。还可以推测，黏膜SRV疫苗在针对志贺氏菌病方面可能特别有效，因为志贺氏菌病会引发人类结肠炎症。
