Oral Vaccination with Attenuated Salmonella typhimurium-Delivered TsPmy DNA Vaccine Elicits Protective Immunity against Trichinella spiralis in BALB/c Mice.
Oral Vaccination with Attenuated Salmonella typhimurium-Delivered TsPmy DNA Vaccine Elicits Protective Immunity against Trichinella spiralis in BALB/c Mice.
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口服疫苗接种减毒鼠伤寒沙门氏菌 TsPmy DNA 疫苗可在 BALB/c 小鼠中引发针对旋毛虫的保护性免疫
DOI：
10.1371/journal.pntd.0004952
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发表时间：
2016-09
影响因子：
3.8
通讯作者：
Zhu X
中科院分区：
文献类型：
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作者：
Wang L;Wang X;Bi K;Sun X;Yang J;Gu Y;Huang J;Zhan B;Zhu X
旋毛虫副肌球蛋白（TsPmy）是一种免疫调节蛋白，可抑制补体C1 q和C8/C9以逃避宿主补体攻击。用重组TsPmy蛋白免疫小鼠，诱导产生了保护性免疫。旋毛虫幼虫攻毒。由于生产TsPmy作为可溶性重组蛋白的困难，我们制备了DNA疫苗作为替代方法，以引起针对旋毛虫感染的强大免疫力。方法：将TsPmy基因的全长编码DNA克隆到真核表达质粒pVAX 1中，转化减毒鼠伤寒沙门氏菌SL 7207。用这种减毒沙门氏菌递送的TsPmy DNA疫苗口服接种小鼠引起肠道中显著的粘膜sIgA应答和以IgG 2a为主要亚类的全身性IgG抗体应答。细胞因子分析还显示，在用TsPmy蛋白刺激后，来自免疫小鼠的脾和MLN的淋巴细胞中的Th 1（IFN-γ、IL-2）和Th 2（IL-4、5、6、10）应答显著增加。抗体分泌型B细胞上归巢受体CCR 9/CCR 10的表达可能与IgA分泌型B细胞向局部肠粘膜的移位有关。用沙门氏菌TsPmy DNA疫苗免疫小鼠，经T.螺旋幼虫结论减毒活链球菌介导的TsPmy DNA经口免疫小鼠，可获得较好的免疫效果。鼠伤寒沙门氏菌引起显著的局部伊加应答和混合的Th 1/Th 2免疫应答，引起显著的抗T.小鼠螺旋体感染。
Background Our previous studies showed that Trichinella spiralis paramyosin (TsPmy) is an immunomodulatory protein that inhibits complement C1q and C8/C9 to evade host complement attack. Vaccination with recombinant TsPmy protein induced protective immunity against T. spiralis larval challenge. Due to the difficulty in producing TsPmy as a soluble recombinant protein, we prepared a DNA vaccine as an alternative approach in order to elicit a robust immunity against Trichinella infection. Methods and Findings The full-length TsPmy coding DNA was cloned into the eukaryotic expression plasmid pVAX1, and the recombinant pVAX1/TsPmy was transformed into attenuated Salmonella typhimurium strain SL7207. Oral vaccination of mice with this attenuated Salmonella-delivered TsPmy DNA vaccine elicited a significant mucosal sIgA response in the intestine and a systemic IgG antibody response with IgG2a as the predominant subclass. Cytokine analysis also showed a significant increase in the Th1 (IFN-γ, IL-2) and Th2 (IL-4, 5, 6, 10) responses in lymphocytes from the spleen and MLNs of immunized mice upon stimulation with TsPmy protein. The expression of the homing receptors CCR9/CCR10 on antibody secreting B cells may be related to the translocation of IgA-secreted B cells to local intestinal mucosa. The mice immunized with Salmonella-delivered TsPmy DNA vaccine produced a significant 44.8% reduction in adult worm and a 46.6% reduction in muscle larvae after challenge with T. spiralis larvae. Conclusion Our results demonstrated that oral vaccination with TsPmy DNA delivered by live attenuated S. typhimurium elicited a significant local IgA response and a mixed Th1/Th2 immune response that elicited a significant protection against T. spiralis infection in mice.
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影响因子：
7.8
作者：
Lin IY;Van TT;Smooker PM
通讯作者：
Smooker PM
旋毛虫副肌球蛋白结合人补体 C1q 并抑制经典补体激活
影响因子：
3.8
作者：
Sun R;Zhao X;Wang Z;Yang J;Zhao L;Zhan B;Zhu X
通讯作者：
Zhu X
DOI：
10.1084/jem.20011910
发表时间：
2002-01-21
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Lamm ME;Phillips-Quagliata JM
通讯作者：
Phillips-Quagliata JM
影响因子：
3.7
作者：
Periaswamy B;Maier L;Vishwakarma V;Slack E;Kremer M;Andrews-Polymenis HL;McClelland M;Grant AJ;Suar M;Hardt WD
通讯作者：
Hardt WD
分泌Iga在肠道中的免疫和粘膜稳态中的复杂角色。
影响因子：
8
作者：
通讯作者：
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