MF59与氢氧化铝佐剂对 HIV-1 gp140三聚体蛋白诱导的体液免疫增强效应的研究  

Evaluation of the efficacy of MF59 and Al （OH） 3 adjuvants in modifying HIV-1 gp140 trimer in-duced specific humoral immune response

作　　者：任莉[1] 朱美玲[1] 侯佳利[1] 刘建东[1] 洪坤学[1] 邵一鸣 郝彦玲[1] 

机构地区：[1]中国疾病预防控制中心性病艾滋病预防控制中心传染病预防控制国家重点实验室,北京102206

出　　处：《中华微生物学和免疫学杂志》2015年第5期367-372,共6页Chinese Journal of Microbiology and Immunology

基　　金：国家科技重大专项（2012ZX10001008,2011ZX09401-019）;传染病预防控制国家重点实验室项目（2012SKL1D103）

摘　　要：目的：研究MF59佐剂与氢氧化铝佐剂对HIV gp140三聚体蛋白诱导HIV抗原特异性体液免疫应答的增强效应，为HIV疫苗寻找更加有效的新型佐剂。方法豚鼠随机分为3组：MF59全剂量组、MF59半剂量组和Al（ OH）3组。于第0、3、6周按抗原佐剂体积比1∶1（ MF59全剂量组）、1∶0．5（MF59半剂量组）和1∶1[Al（OH）3组]免疫豚鼠，第9周取血分离血清。 ELISA间接法检测血清抗HIV-1 gp120结合抗体和抗HIV-1 gp70V1V2结合抗体，TZM-bl假病毒方法检测血清对4个亚型8个假病毒的中和抗体。结果 HIV-1 gp120结合抗体滴度，MF59全剂量组与MF59半剂量组均显著高于Al（OH）3组（P＝0．027和P＝0．041）；HIV-1 gp70V1V2结合抗体A405读数MF59全剂量组显著高于Al（OH）3组（P＝0．029），MF59半剂量组与Al（OH）3组比较差异无统计学意义（P＝0．34）。假病毒中和活性检测，除去MF59半剂量组不能中和B亚型的两个假病毒REJO4541和TR-JO4551外，各组对8个假病毒均有不同强度的中和活性。8个假病毒中和活性半数抑制剂量（ ID50）的几何平均值比较：MF59全剂量组＞Al（ OH）3组＞MF59半剂量组。结论与传统的氢氧化铝佐剂相比，全剂量的MF59佐剂与HIV-1 gp140三聚体蛋白共同免疫豚鼠，血清抗原特异性结合抗体的水平显著提高，中和抗体的水平亦有提高的趋势。Objective To evaluate the effectiveness of MF59 and Al（ OH） 3 adjuvants in potentia-ting HIV-1 specific humoral immune response when used in combination with HIV-1 gp140 trimer.Methods Guinea pigs were randomly divided into three groups including the MF59 full dose treatment group （ antigen to adjuvant volume ratio：1 ∶1 ） , the MF59 half dose treatment group （ antigen to adjuvant volume ratio：1 ∶0.5） and the Al（OH）3 treatment group （antigen to adjuvant volume ratio：1 ∶1）.The guinea pigs in each group were immunized with gp140 trimer and corresponding adjuvants for three times with three weeks interval between each injection.Serum samples were collected at week 9 for the detection of HIV-1 gp120 binding antibodies, HIV-1 gp70V1V2 binding antibodies and HIV-1 neutralizing antibodies against eight dif-ferent pseudoviruses of four different clades.Results Compared with the Al（OH）3 treatment group, the guinea pigs treated with full dose and half dose of MF59 showed significantly increased titers of HIV-1 gp120 binding antibodies （P=0.027 and P=0.041）.The levels of HIV-1 gp70V1V2 binding antibodies in full dose of MF59 treated guinea pigs were significantly higher than those of Al（ OH） 3 treated guinea pigs （ P=0.029）.No significant difference with the HIV-1 gp70V1V2 binding antibodies was observed between the MF59 half dose treatment group and the Al（ OH） 3 treatment group.The serum samples collected from each group could neutralize the eight different pseudoviruses at different degrees, except that two pseudoviruses of clade B （ REJO4541 and TRJO4551） could not be neutralized by serum samples from MF59 half dose treated guinea pigs.The MF59 full dose treatment group showed the highest geometric mean of 50%inhibitory dosenbsp;（ID50） to the eight pseudoviruses, followed by Al（OH）3 treatment group and MF59 half dose treatment group.Conclusion Compared with the traditional Al（OH）3 adjuvant, full dose of MF59 adjuvant in com-bination with HIV-1 gp140 trim

关 键 词：MF59 氢氧化铝 HIV-1 HIV特异性抗体 佐剂 

分 类 号：R392[医药卫生—免疫学]