不同HBsAg疫苗联合免疫后诱导小鼠细胞和体液免疫应答的研究

目的：了解HBsAg的蛋白疫苗（P）、痘苗病毒疫苗（V）、DNA疫苗（D）联合免疫小鼠诱导的特异性体液和细胞免疫应答。方法：以P、V或D疫苗中的一种疫苗初次免疫BALB／c小鼠后，于第2、5、8、11周再用另一种疫苗加强，共产生9种免疫组合：即PP、PV、PD、VP、VV、VD、DP、DV及DD。于初免后第2、5、8、11周采血检测血清中抗HBsAgIgG的总滴度及其IgG1和IgG2a亚类，并于每次加强免疫后第7天，检Nd,鼠脾脏的CTL对P815S细胞的特异性杀伤率。结果：在P、V、D3种疫苗中，V疫苗诱导产生抗HBsAg抗体的速度最快，P疫苗诱导的体液免疫回忆反应最强，D疫苗诱导产生的抗体最弱。除PP疫苗组合诱导的抗体明显倾向于IgG1外，其他均无明显的倾向性。各种免疫组合中，VD和DV疫苗组诱导的CTL应答最强，对P815S的特异性杀伤率分别为71％和64％。结论：在各种联合免疫组合中，PV、PD、VP和VD疫苗组的抗体应答较好；而DV和VD疫苗组诱导的CTL杀伤效应最强。

Immune response induced by combinant immunization of different HBsAg vaccines in mice

AIM: To investigate the specific humoral and cellular immune response induced by prime-boost immunization of HBsAg protein vaccine (P), recombinant vaccinia virus vaccine (V) and DNA vaccine (D) in mice. METHODS: Groups of BALB/c mice were primed by one of the three vaccines P, V or D and boosted by another vaccine at 2, 5, 8 and 11 week later, thus 9 immune combinations were made: PP, PV, PD, VP, VV, VD, DP, DV and DD. Serum samples were collected at week 2, 5, 8 and 11 and levels of anti-HBsAg IgG antibodies and their sub-isotypes were determined. Seven days after every boost, spleen cells of vaccinated mice were separated and the specific CTL lysis ratio of P815S cells were determined. RESULTS: Among the three HBsAg vaccines P, V and D, V could induce the quickest humoral immune response. The memory humoral immune response induced by P was the strongest. D induced the weakest antibody titer. The ratio of specific IgG1/IgG2a indicated that antibody induced by PP was more polarized to Th2. The other groups induced balanced Th1/Th2 immune response. Among all the groups, VD and DV induced the strongest CTL response, and the specific lysis ratio of P815S cells was 71% and 64%, respectively. CONCLUSION: The exprimental results suggested that among all the immune combinations, PV, PD, VP and VD can induce better humoral immune response while DV and VD can induce stronger CTL response in BALB/c mice.