3种市售免疫调节剂作为流感病毒融合蛋白NM2e亚单位疫苗佐剂的研究

目的:观察具有免疫调节作用的市售左旋咪唑、西米替丁、伐地那非作为甲型流感病毒核蛋白(NP)与基质蛋白2胞外区多肽(M2e)融合蛋白NM2e亚单位疫苗佐剂的可能性。方法:将左旋咪唑、西米替丁、伐地那非单独或者分别与Al(OH)3配伍作为NM2e蛋白佐剂,经肌肉注射免疫BALB/c小鼠,通过体液和细胞免疫检测及病毒攻击实验研究这些免疫调节剂作为疫苗佐剂的可能性。结果:左旋咪唑对NM2e蛋白亚单位疫苗无明显的佐剂效应,但与铝佐剂合用可使攻毒后存活小鼠体重恢复加快;西米替丁可以明显提高NM2e蛋白诱发的特异性IgG2a滴度,提高攻毒后小鼠的存活率(30%),但保护效果明显低于铝佐剂(70%),与铝佐剂无明显的协同作用;伐地那非能明显增加NM2e蛋白诱发的特异性IgG1、IgG2a滴度,提高攻毒后小鼠的存活率(36%),但与铝佐剂合用有相互抑制作用。结论:左旋咪唑、西米替丁、伐地那非对NM2e蛋白均有一定的免疫调节作用,其中西米替丁和伐地那非能提高攻毒保护效果,但保护效果明显低于Al(OH)3,与Al(OH)3联合使用均无协同作用。

Study on the Probability of Three Commercially Available Immunomodulators Used as the Adjuvant of a Subunit Vaccine of Influenza Virus Fusion Protein NM2e

Objective： To evaluate the probability of three commercially available immunoregulatory medicines, levamisole, cimetidine and vardenafil, to be used as the adjuvant of a subunit vaccine of influenza virus fusion protein NM2e, NP fused with M2e. Methods： BALB / c mice were immunized intramuscularly with NM2e protein formulated with levamisole, cimetidine and vardenafil individually or together with Al（OH）3, humoral and cellular immunoresponse and virus challenge experiment were analyzed, and the probability of the above mentioned immunoregulatory medicines used as vaccine adjuvant were evaluated. Results： Levamisole didn＇t show obvious adjuvant effect for subunit vaccine of NM2e protein, however, levamisole plus Al（OH）3 could accelerate weight recovery of virus challenged mice; cimetidine could clearly increase serum IgG2a titer and percent survival of challenged mice（30%） induced by NM2e protein, however it was significantly lower than that induced by Al（OH）3 adjuvanted NM2e protein（70%）, and it didn＇t show the synergy between cimitidine and Al （OH）3; vardenafil could increase serum IgG1 and IgG2a titers and percent survival induced by NM2e protein（36%） clearly, however it inhibited the adjuvant effect of Al（OH）3. Conclusion： Levamisole, cimetidine and vardenafil showed certain immunoregulatory effects on NM2e protein, cimetidine and vardenafil could improve protective effect induced by NM2e protein in virus challenge experiment, however the protective effects were obviously poorer than that induced by Al（OH）3 adjuvanted NM2e protein, and it didn＇t show the synergy between cimetidine / vadenafil and Al（OH）3.