The Immunogenicity of CRISP1 Plasmid-Based Contraceptive Vaccine can be Improved When Using Chitosan Nanoparticles as the Carrier
The Immunogenicity of CRISP1 Plasmid-Based Contraceptive Vaccine can be Improved When Using Chitosan Nanoparticles as the Carrier
复制标题
以壳聚糖纳米粒为载体可提高CRISP1质粒避孕疫苗的免疫原性
DOI：
10.1111/aji.12513
复制
发表时间：
2016
影响因子：
3.6
通讯作者：
Yang J
中科院分区：
文献类型：
--
作者：
Luo Jin;Liu Xue-li;Zhang Yi;Wang Ya-qin;Xu Wang-ming;Yang Jing;Yang J
问题为评价以编码小鼠CRISP 1的质粒DNA为抗原，壳聚糖纳米颗粒为载体的避孕疫苗的有效性和安全性，研究方法制备壳聚糖-pcDNA 3. 1-mCRISP 1纳米颗粒（CS-DNA NPs），并对其形态、zeta电位、多分散指数和pDNA结合能力进行表征。与Lipofectamine 2000™相比，在COS-7细胞中评估CS-DNA NP的细胞毒性和基因转移能力。四组小鼠分别接受0.9%生理盐水、pcDNA3.1载体、pcDNA3.1-CRISP 1或CS-DNA NP的三次注射。ELISA法检测免疫应答。结果CS-DNA纳米颗粒呈球形或椭圆形，平均直径为189.3 nm，zeta电位为正，DNA凝聚良好。它还显示出高的DNA酶抗性和良好的转染效率，而没有细胞毒性。CS-DNA NP免疫小鼠的抗mCRISP 1抗体滴度显著高于pcDNA3.1-CRISP 1组。结论以壳聚糖-DNA纳米颗粒为载体制备的mCRISP 1 DNA避孕疫苗具有较好的免疫原性和安全性。
ProblemTo evaluate the effectiveness and security of a contraceptive vaccine using plasmid DNA encoding mouse CRISP1 as antigen and chitosan nanoparticles as the carrier.Method of studyChitosan‐pcDNA3.1‐mCRISP1 Nanoparticles (CS‐DNA NPs) were prepared and characterized in terms of morphology, zeta potential, polydispersity index, and binding capacity of pDNA. The cytotoxicity and gene transfer capability of CS‐DNA NPs were assessed in COS‐7 cells compared to Lipofectamine 2000™. Four groups of mice received three injections of 0.9% normal saline, pcDNA3.1 vector, pcDNA3.1‐CRISP1, or CS‐DNA NPs, respectively. ELISA was used to examine the immune responses. Fertility and mean litter size were analyzed by natural mating.ResultsCS‐DNA NPs have a spherical or elliptical shape with a mean diameter of 189.3 nm, positive zeta potential, and good DNA condensation. It also showed high DNAse resistance and good transfection efficiency without cell toxicity. The titers of anti‐mCRISP1 antibodies from CS‐DNA NP‐immunized mice were significantly higher than that of pcDNA3.1‐CRISP1 group. Male and female CS‐DNA NP‐immunized animals were recognized with a statistically significant reduction in their fertility compared with pcDNA3.1‐CRISP1‐immunized mice.ConclusionThis study demonstrated that using chitosan‐DNA nanoparticles as the carrier can improve the immunogenicity of mCRISP1 DNA contraceptive vaccine with good security.