Induction of long-lasting protective immunity against Toxoplasma gondii in BALB/c mice by recombinant surface antigen 1 protein encapsulated in poly (lactide-co-glycolide) microparticles.
Induction of long-lasting protective immunity against Toxoplasma gondii in BALB/c mice by recombinant surface antigen 1 protein encapsulated in poly (lactide-co-glycolide) microparticles.
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DOI：
10.1186/1756-3305-6-34
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发表时间：
2013-02-11
影响因子：
3.2
通讯作者：
Yang CD
中科院分区：
文献类型：
--
作者：
Chuang SC;Ko JC;Chen CP;Du JT;Yang CD
弓形虫是弓形虫病的病原体，目前针对弓形虫的亚单位疫苗的研究主要集中在速殖子表面抗原1（SAG 1）上。由于由聚（丙交酯-共-乙交酯）（PLG）聚合物制成的微粒已被开发为安全、有效的佐剂或递送系统，我们的目的是用PLG聚合物包封重组SAG1（rSAG1）以制备PLG包封的rSAG1（PLG-rSAG1）微粒，其将维持rSAG1释放并产生针对T. BALB/c小鼠弓形虫感染。在本研究中，rSAG1被封装到PLG微粒通过复乳法。然后将PLG-rSAG1微粒以14天的间隔腹膜内注射到BALB/c小鼠中两次。我们检查了PLG-rSAG1微粒诱导和延长有效抗弓形虫免疫应答的能力，与用Vet L-10佐剂配制的rSAG1（Vet L-10））进行比较。在最后一次免疫后8周，还在1 × 104活T的致死皮下攻击后评价保护活性。弓形虫速殖子PLG-rSAG1微球粒径为4.25~6.58 μ m，包封率为69%~81%。从微粒释放的rSAG1蛋白的量在35天内逐渐增加，并且蛋白质仍然保留天然SAG1抗原性。用微粒腹膜内接种小鼠导致增强的SAG1特异性IgG滴度以及淋巴细胞增殖，更重要的是，这些增强的活性维持了10周。此外，在最后一次免疫后8周，在用PLG-rSAG 1微粒免疫的小鼠中检测到γ干扰素的最大产生。此外，80%（8/10）的用PLG-rSAG1微粒免疫的小鼠在致死性皮下速殖子攻击后存活至少28天。将rSAG1包封到PLG微粒中保留了天然SAG1抗原性并维持rSAG1从微粒中释放。PLG-rSAG1微粒不仅能有效诱导SAG1特异性的体液和细胞免疫应答，而且能有效保护T.弓形虫速殖子感染本研究为开发长效T.供将来用于人类和动物。
Current development efforts of subunit vaccines against Toxoplasma gondii, the etiological agent of toxoplasmosis, have been focused mainly on tachyzoite surface antigen 1 (SAG1). Since microparticles made from poly (lactide-co-glycolide) (PLG) polymers have been developed as safe, potent adjuvants or delivery systems, we aimed to encapsulate recombinant SAG1 (rSAG1) with the PLG polymers to prepare PLG-encapsulated rSAG1 (PLG-rSAG1) microparticles that would sustain rSAG1 release and generate long-lasting protective immunity against T. gondii in BALB/c mice. In the present study, rSAG1 was encapsulated into PLG microparticles by the double emulsion method. PLG-rSAG1 microparticles were then intraperitoneally injected twice at a 14-day interval into BALB/c mice. We examined the ability of PLG-rSAG1 microparticles to induce and prolong effective anti-Toxoplasma immune responses, in comparison with rSAG1 formulated with a Vet L-10 adjuvant (rSAG1 (Vet L-10)). Eight weeks after the last immunization, protective activities were also evaluated after a lethal subcutaneous challenge of 1x104 live T. gondii tachyzoites. PLG-rSAG1 microparticles, 4.25~6.58 micrometers in diameter, showed 69%~81% entrapment efficiency. The amount of released rSAG1 protein from microparticles increased gradually over a 35-day period and the protein still retained native SAG1 antigenicity. Intraperitoneal vaccination of mice with the microparticles resulted in enhanced SAG1-specific IgG titers as well as lymphocyte proliferation and, more importantly, these enhanced activities were maintained for 10 weeks. In addition, eight weeks after the last immunization, maximum production of gamma interferon was detected in mice immunized with PLG-rSAG1 microparticles. Furthermore, 80% (8/10) of mice immunized with PLG-rSAG1 microparticles survived at least 28 days after a lethal subcutaneous tachyzoite challenge. Encapsulation of rSAG1 into PLG microparticles preserves the native SAG1 antigenicity and sustains the release of rSAG1 from microparticles. PLG-rSAG1 microparticles can effectively induce not only significant long-lasting SAG1-specific humoral and cell-mediated immune responses but also high protection against T. gondii tachyzoite infection. Our study provides a valuable basis for developing long-lasting vaccines against T. gondii for future use in humans and animals.
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影响因子：
14.2
作者：
Hill, D;Dubey, JP
通讯作者：
Dubey, JP
影响因子：
5.5
作者：
Byrd, W;Cassels, FJ
通讯作者：
Cassels, FJ
影响因子：
4
作者：
Grimwood, J;Smith, JE
通讯作者：
Smith, JE
影响因子：
4.4
作者：
Kang, H;Remington, JS;Suzuki, Y
通讯作者：
Suzuki, Y
影响因子：
3.1
作者：
Johnson, LL;Sayles, PC
通讯作者：
Sayles, PC