非复制型多价重组痘苗病毒粘膜与细胞免疫效果

MUCOSAL AND CELLULAR IMMUNE RESPONSES OF NON REPLICATING MULTIVALENT VACCINIA RECOMBINANT VIRUS

对已构建的同时表达乙型肝炎病毒ＳＳ１、麻疹病毒ＨＡ和Ｆ以及ＩＬ２的非复制型重组痘苗病毒ＶＨＦＩＬ２ΔＣＫＳＳ１，及其相应的复制型重组病毒ＶＨＦＩＬ２ＳＳ１，进行了兔皮内毒力、粘膜免疫和细胞免疫效果的比较研究。发现ＶＨＦＩＬ２ΔＣＫＳＳ１在兔皮内的毒力明显低于ＶＨＦＩＬ２ＳＳ１。ＶＨＦＩＬ２ΔＣＫＳＳ１经空肠内免疫家兔４周后，可在肠粘膜表面诱发特异性ＩｇＡ抗体，在血液中诱发特异性的ＩｇＧ抗体，其抗ＳＳ１和抗麻疹病毒ＩｇＡ和ＩｇＧ的抗体滴度与ＶＨＦＩＬ２ＳＳ１免疫组相同，抗痘苗病毒ＩｇＧ抗体比ＶＨＦＩＬ２ＳＳ１免疫组低１６倍。ＶＨＦＩＬ２ΔＣＫＳＳ１经腹腔注射免疫４周的小鼠脾细胞，可在体外刺激产生高水平的麻疹病毒及痘苗病毒特异性ＣＴＬ，与ＶＨＦＩＬ２ＳＳ１无显著性差异。这些结果初步证实了非复制型痘苗病毒载体作为多价疫苗载体的有效性及安全性。

The investigation reported in this paper focused on the comparison of virulence, mucosal and cellular immunological effects between the non replicating recombinant VHFIL2Δ CKSS1 and the replicating recombinant VHFIL2SS1 that can express the SS1 protein of HBV, the HA and F proteins of measles virus and the IL2. The virulence of VHFIL2ΔCKSS1 was obviously less than that of VHFIL2SS1 in rabbit skin. By intrajejunal immunization, VHFIL2Δ CKSS1 could bring about both the specific IgA antibody on mucosal surface of jejunum and the IgG in blood of rabbits after 4 weeks. The titer of antibodies against SS1 antigen and measles virus were as same as that induced by VHFIL2SS1, while the anti vaccinia IgG in blood was 16 times less. By intraperitoneal immunization, the spleen cells of mice could be stimulated in vitro by measles and vaccinia viruses to produce specific CTL at a significant level which did not show difference between VHFIL2ΔCKSS1 and VHFIL2SS1. These results confirm the efficacy and safety of non replicating vaccinia virus as a vector of multivalent vaccine.