B群脑膜炎球菌外膜蛋白0315不同形式疫苗免疫效果比较

发布时间：2019-08-26 16:12

【摘要】：目的:初步探讨和评价NMB0315核酸疫苗、重组蛋白疫苗及核酸疫苗+重组蛋白疫苗联合免疫诱导小鼠产生的特异性体液/细胞免疫应答水平及其免疫保护效果,为进一步探索NMB0315疫苗有效的免疫方法和途径提供实验依据。方法:大量制备核酸疫苗[pc DNA3.1(+)/NMB0315]和重组蛋白疫苗(p ET-30a/NMB0315),采用核酸初免-蛋白加强的方法联合免疫或分别免疫雌性BALB/c小鼠,测定特异性体液/细胞免疫应答水平、免疫血清体外杀菌效价,观察疫苗对感染B群脑膜炎球菌小鼠的免疫保护效果。结果:NMB0315核酸疫苗组(p NMB0315-Cp G)、蛋白疫苗组(r NMB0315-FA)及联合免疫疫苗组(p NMB0315-Cp G+r NMB0315-FA)诱导的血清特异性Ig G、Ig G1、Ig G2a及生殖道灌洗液中特异性s Ig A水平在第八周达到峰值,A450值分别为(0.505±0.042、0.513±0.022、0.342±0.017、0.250±0.015)、(0.823±0.061、0.807±0.045、0.596±0.027、0.450±0.028)和(0.694±0.053、0.711±0.032、0.455±0.021、0.386±0.024),明显高于PBS对照组(P0.01);其中,蛋白疫苗组的抗体水平明显高于联合免疫疫苗组和核酸疫苗组(P0.05)。小鼠脾淋巴细胞刺激指数及IFN-γ水平,联合免疫疫苗组明显高于蛋白疫苗组和核酸疫苗组(P0.05);核酸疫苗组、蛋白疫苗组和联合免疫疫苗组免疫血清在补体介导下的体外杀菌抗体效价分别为1∶64、1∶128和1∶128,对实验小鼠的免疫保护率分别为70%、95%和80%。免疫2、4、6、8周时,核酸疫苗组、重组蛋白疫苗组和联合免疫疫苗组Ig G2a/Ig G1比值均小于1。结论:NMB0315疫苗诱导的体液免疫(包括黏膜免疫)效果从高到低为:重组蛋白疫苗组、联合免疫疫苗组、核酸疫苗组;诱导细胞免疫的效果从高到低为:联合免疫疫苗组、核酸疫苗组、重组蛋白疫苗组;NMB0315疫苗对实验小鼠的免疫保护效果从高到低为:重组蛋白疫苗组、联合免疫疫苗组、核酸疫苗组。
[Abstract]:Objective: To study and evaluate the specific humoral/ cellular immune response level and the immune protective effect of NMB0315 nucleic acid vaccine, recombinant protein vaccine and nucleic acid vaccine + recombinant protein vaccine in mice. To provide an experimental basis for further exploring the effective immunization methods and methods of the NMB0315 vaccine. Methods: A large amount of nucleic acid vaccine (pcDN1 (+)/ NMB0315] and recombinant protein vaccine (pET-30a/ NMB0315) were prepared. To observe the effect of the vaccine on the immune protection of B-group meningococcal mice. Results: The serum specific Ig G, Ig G1, Ig G2a and the specific s Ig A level in the NMB0315 nucleic acid vaccine group (pNMB0315-Cp G), the protein vaccine group (r NMB0315-FA) and the combined immune vaccine group (p NMB0315-Cp G + r NMB0315-FA) reached the peak at the eighth week, A450 values were (0.505, 0.042, 0.513, 0.022, 0.342, 0.017, 0.250, 0.015), (0.823, 0.061, 0.807, 0.045, 0.596, 0.027, 0.450, 0.028), and (0.694, 0.053, 0.711, 0.032, 0.455, 0.021, 0.386, 0.024), respectively, significantly higher than in the PBS control group (P0.01); in which the level of antibody in the protein vaccine group was significantly higher than that of the combined immunovaccine group and the nucleic acid vaccine group (P0.05). The titer of the in vitro bactericidal antibody against the complement-mediated by the immune serum of the nucleic acid vaccine group, the protein vaccine group and the combined immune vaccine group was 1:64,1:128 and 1:128, respectively. The immune protection rate of the experimental mice was 70%,95% and 80%, respectively. The ratio of Ig G2a/ Ig G1 in the nucleic acid vaccine group, the recombinant protein vaccine group and the combined immune vaccine group was less than 1 at the 2,4,6 and 8 weeks of immunization. Conclusion: The humoral immunity (including mucosal immunity) induced by the NMB0315 vaccine is from high to low: the recombinant protein vaccine group, the combined immune vaccine group and the nucleic acid vaccine group; the effect of inducing the cell immunity is from high to low: the combined immune vaccine group, the nucleic acid vaccine group and the recombinant protein vaccine group; The immune protective effect of the NMB0315 vaccine against the experimental mice is from high to low: the recombinant protein vaccine group, the combined immune vaccine group and the nucleic acid vaccine group.
【作者单位】：南华大学病原生物学研究所;长沙市疾病预防控制中心;
【基金】：国家自然科学基金(81172890) 特殊病原体防控湖南省重点实验室(湘科计字2014-5号、湘教通2012-312号) 湖南省分子靶标药物研究协同创新中心资助
【分类号】：R392

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