Construction, characterization and evaluation of the protective efficacy of the Streptococcus suis double mutant strain Delta SsPep/Delta SsPspC as a live vaccine candidate in mice
Construction, characterization and evaluation of the protective efficacy of the Streptococcus suis double mutant strain Delta SsPep/Delta SsPspC as a live vaccine candidate in mice
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猪链球菌双突变株 Delta SsPep/Delta SsPspC 作为小鼠活疫苗候选物的构建、表征和保护功效评估
DOI：
10.1016/j.micres.2014.08.010
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发表时间：
2015
影响因子：
6.7
通讯作者：
Bei Weicheng
中科院分区：
文献类型：
--
作者：
Hu Jin;You Wujin;Wang Bin;Hu Xueying;Tan Chen;Liu Jinlin;Chen Huanchun;Bei Weicheng
猪链球菌2型（S. suis 2）在仔猪和人类中引起败血症和脑膜炎，并导致影响全世界商品猪生产的最严重的细菌性疾病之一。由于目前的灭活疫苗不能有效预防该病，因此需要研制一种新的减毒活疫苗。迫切需要通过删除必需的毒力因子来获得SUIS 2。我们已经报道了基于S. suis2.我们的前期研究表明SsPepe在S. suis2.在本研究中，一个精确定义的双缺失突变体ΔSsPep/Δ SsPspp Δ S.利用ΔSsPep构建了不带抗性标记的suis 2，并在小鼠实验感染模型中比较了野生型和ΔSsPep/Δ SsPspC的毒力水平。我们证明了双突变体ΔSsPep/Δ SsPspC的毒力低于WT，并且可以诱导显著的抗体应答。IgG亚类（IgG 1和IgG 2a）的分析表明，ΔSsPep/ΔSsPspC诱导了Th 1和Th 2应答，但IgG 2a（Th 1）应答占优势，IgG 1（Th 2）应答占优势。ΔSsPep/Δ SsPspC在致死剂量下对攻击的保护率可达90%。suis2.综上所述，这些数据表明ΔSsPep/Δ SsPspC可以用作有效的活疫苗，并提供了一种新的抗S. suis2.
Streptococcus suisserotype 2 (S. suis2) causes sepsis and meningitis in piglets and humans, and results in one of the most serious bacterial diseases affecting the production of commercial pigs around the world. Due to the failure of the current inactivated vaccine to protect against the disease, development of a new attenuated live vaccine againstS. suis2 by deleting essential virulence factors is urgently needed. We have previously reported the construction and characterization of anSsPepsingle gene deletion mutant strain ΔSsPepbased onS. suis2. Our previous results have shown thatSsPepplays a critical role in the pathogenesis ofS. suis2. In this study, a precisely defined double-deletion mutant ΔSsPep/ΔSsPspCofS. suis2 without antibiotic-resistance markers was constructed based on ΔSsPep, and the levels of virulence of the wild-type (WT) and ΔSsPep/ΔSsPspCwere compared in a mouse experimental infection model. We demonstrated that the double mutant ΔSsPep/ΔSsPspCwas less virulent than the WT, and could induce a noticeable antibody response. Analysis of IgG subclasses (IgG1 and IgG2a) indicated that both Th1 and Th2 responses were induced by ΔSsPep/ΔSsPspC, although the IgG2a (Th1) response predominated over the IgG1 (Th2) response. Moreover, ΔSsPep/ΔSsPspCcould confer 90% protective efficacy against challenge with a lethal dose of fully virulentS. suis2. Taken together, these data demonstrate that ΔSsPep/ΔSsPspCcan be used as an effective live vaccine and provide a novel strategy against infection ofS. suis2.