Intranasal immunization with recombinant PspA fused with a flagellin enhances cross-protective immunity against Streptococcus pneumoniae infection in mice
Intranasal immunization with recombinant PspA fused with a flagellin enhances cross-protective immunity against Streptococcus pneumoniae infection in mice
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DOI：
10.1016/j.vaccine.2011.05.095
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发表时间：
2011-08-05
期刊：
影响因子：
5.5
通讯作者：
Rhee, Joon Haeng
中科院分区：
文献类型：
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作者：
Chung Truong Nguyen;Kim, Soo Young;Rhee, Joon Haeng
肺炎链球菌是一种主要的呼吸道病原体，在婴儿和老年人中造成高死亡率和发病率。尽管使用了抗生素和疫苗，致命的肺炎球菌疾病仍然普遍存在。肺炎球菌表面蛋白A （PspA）是一种由所有肺炎链球菌菌株产生的高度免疫原性表面蛋白，可引起对致命肺炎球菌感染的保护性免疫。我们之前已经证明，创伤弧菌FlaB是一种细菌鞭毛蛋白和TLR5的激动剂，具有很强的粘膜佐剂活性，并在与破伤风类毒素共给药时诱导保护性免疫。在这项研究中，我们测试了用由PspA和FlaB组成的重组融合蛋白（PspA-FlaB和FlaB-PspA）进行鼻内免疫是否能够比单独使用PspA或PspA和FlaB的化学计量混合物免疫更有效地引发针对肺炎球菌感染的保护性粘膜免疫反应。用融合蛋白鼻内免疫小鼠后，血清和粘膜分泌物中抗pspa IgG和IgA水平显著升高。与仅用PspA、PspA和FlaB的混合物或PspA-FlaB融合蛋白免疫的小鼠相比，经鼻内接种FlaB-PspA融合蛋白的小鼠对活的肺炎链球菌的致命攻击保护最大。FlaB-PspA对异源荚膜类型也有交叉保护作用。这些结果表明，FlaB-PspA融合蛋白可以单独作为抗肺炎球菌粘膜疫苗或作为多价荚膜多糖结合疫苗的有效伴侣蛋白。(C) 2011 Elsevier Ltd.版权所有。
Streptococcus pneumoniae is a major respiratory pathogen that causes high levels of mortality and morbidity in infants and the elderly. Despite the use of antibiotics and vaccines, fatal pneumococcal disease remains prevalent. Pneumococcal surface protein A (PspA), a highly immunogenic surface protein produced by all strains of S. pneumoniae, can elicit protective immunity against fatal pneumococcal infection. We have previously demonstrated that the Vibrio vulnificus FlaB, a bacterial flagellin protein and agonist of TLR5, has strong mucosal adjuvant activity and induces protective immunity upon co-administration with tetanus toxoid. In this study, we have tested whether intranasal immunization with recombinant fusion proteins consisted of PspA and FlaB (PspA-FlaB and FlaB-PspA) is able to elicit more efficient protective mucosal immune responses against pneumococcal infection than immunization with PspA alone or with a stoichiometric mixture of PspA and FlaB. When mice were intranasally immunized with fusion proteins, significantly higher levels of anti-PspA IgG and IgA were induced in serum and mucosal secretions. The mice immunized intranasally with the FlaB-PspA fusion protein were the most protected from a lethal challenge with live S. pneumoniae, as compared to the mice immunized with PspA only, a mixture of PspA and FlaB, or the PspA-FlaB fusion protein. FlaB-PspA also induced a cross protection against heterologous capsular types. These results suggest that a FlaB-PspA fusion protein alone could be used as an anti-pneumococcal mucosal vaccine or as an effective partner protein for multivalent capsular polysaccharide conjugate vaccines. (C) 2011 Elsevier Ltd. All rights reserved.