目的  研究含前S表位重组HBsAg（SS1S2）与重组HBcAg（C）联合免疫BALB/c小鼠的体液和细胞免疫应答。 方法   用纯化的SS1S2与C分别配制含或不含Al(OH)3佐剂（Al）的疫苗。采用简单随机法将雌性BALB/c小鼠分为5组：阴性对照（NC）、SS1S2、SS1S2+C、SS1S2+Al、SS1S2+C+Al，各组分别于0和21 d进行腹腔免疫，对照组注射磷酸盐缓冲液。初免及加强后1周各取一半小鼠采血，采用ELISA法测定抗-HBs、抗-前S1、抗-前S2和抗-HBc滴度；常规制备脾淋巴细胞，用酶联免疫斑点法测定分泌IFN-γ的T细胞频数。采用t检验对各组结果进行比较。 结果   联合HBcAg的疫苗组均产生了较高水平的抗-HBs、抗-前S1、抗-前S2和抗-HBc。初免后1周，SS1S2+C组的抗-HBs阳转比例（1/5）高于SS1S2组（0/5）、SS1S2+Al+C组（4/5）高于SS1S2+Al组（3/5）；SS1S2+C组的抗-前S1阳转比例（3/5）高于SS1S2组（0/5）；HBcAg对抗-前S2的产生无影响。加强免疫后，各疫苗组的抗体滴度均升高，联合HBcAg的疫苗组各抗体滴度明显高于SS1S2疫苗组。各组疫苗免疫后均可诱导细胞免疫应答，初免后SS1S2+C和SS1S2+Al+C组分泌IFN-γ的T细胞频数显著超过SS1S2和S1S2+Al组（t值分别为2.926、2.974，P值均<0.05）；加强免疫后，各组均有加强效应，SS1S2+C组的T细胞频数明显超过SS1S2组（t=4.604，P=0.010）。 结论   SS1S2联合HBcAg可在BALB/c小鼠中诱导较强的免疫应答，HBcAg可增强SS1S2诱导的体液及细胞免疫应答。

 Objective  To study humoral and cellular mediated immune response (CMI) to recombinant HBsAg containing PreS epitopes (SS1S2) combined with recombinant HBcAg (C) in BALB/c mice.  Methods   Female BALB/c mice were divided into 5 groups by a simple random method and intraperitoneally immunized with SS1S2, SS1S2+C, SS1S2+Al(OH)3 (Al) and SS1S2+C+Al, respectively, at days 0 and 21. PBS was used as control. Blood and spleen were taken 1 week after primary and boost injections. Serum titers of anti-HBs, anti-PreS1, anti-PreS2 and anti-HBc were detected by ELISA. Spleen-lymphocytes were isolated and frequency of IFN-γ-Secreting T cells was measured by enzyme-linked immunospot assay. The results were analyzed by t-test.  Results   High levels of anti-HBc, anti-HBs, anti-PreS1 and anti-PreS2 were induced in both groups immunized with HBcAg. One week after primary immunization, the seroconversion ratios of anti-HBs in SS1S2+C (1/5) and SS1S2+C+Al (4/5) groups were higher than those in SS1S2 (0/5) and SS1S2+Al (3/5) groups, respectively. The seroconvesion ratio of anti-PreS1 in SS1S2+C group (3/5) was higher than that in SS1S2 group (0/5). The production of anti-preS2 was not influenced by combination with HBcAg. After boost, the levels of anti-HBs, anti-PreS1 and anti-PreS2 in groups with HBcAg were higher than those in groups without HBcAg. All vaccine groups generated CMI response. One week after primary immunization, the frequency of IFN-γ-secreting T cells in SS1S2+C and SS1S2+Al+C groups was higher than those in SS1S2 and S1S2+Al groups (t=2.926, 2.974, P<0.05). After boost, the T cells in SS1S2+C group was significantly higher than that in SS1S2 group (t=4.604, P=0.010).  Conclusions   SS1S2 combined with HBcAg has strong immunogenicity in mice and HBcAg could enhance humoral and CMI responses to SS1S2.