Hu Zhong-yu, He Peng, Fang Xin, Qiu Shao-hui, Liang Zheng-lun, Li He-min, Zhuang Hui
National Institute for Control of Pharmaciutical and Biological Products, Beijing 100050, China.
Zhonghua Liu Xing Bing Xue Za Zhi. 2008 Aug;29(8):810-4.
To evaluate the kinesis of cellular and humoral immune responses to different kinds of recombinant hepatitis B(rHB) vaccines in the immunized mice.
At serial time points, the levels of IFN-gamma and IL-2 secreted by spleens mononuclear cells (MNC) of the vaccinated mice were detected by enzyme-linked immunospot methods (ELISPOT) after stimulation in vitro with HBsAg MHC class I peptide S28-39 or HBsAg. The lymphocytotoxicity of the immunized mice were also detected (CTL) by a specific lysis assay and the levels of anti-HBs were measured by the Abbott IMX kit.
The peak values of IFN-gamma and IL-2 in vaccinated mice were detected by ELISPOT, 10 - 14 days after immunization. The CTL and the level of IFN-gamma induced by rHB vaccine derived from yeast cells (Hansenula polymorpha) (rHP vaccine) were significantly higher than the other two vaccines (P < 0.05). The maximum lysis of CTL appeared in the vaccinated mice on day 10 after immunization, with the percentage of 39.8%. The levels of IL-2 induced by rHP vaccine were significantly higher than the other two vaccines (P < 0.05). However, the IL-2 levels in the rSC (saccharomyces cerevisiae) vaccine group were higher as compared with the rCHO vaccine group at day 7 and day 14 (7 d t = 4.595, P = 0.001 < 0.05; 14 d t = 5.721, P = 0.000 < 0.05) after immunization. The cellular immune response to the rHP vaccine was the strongest while it was the lowest to the rCHO vaccine at day 7 after immunization. The sero-positive rates and the titers of anti-HBs in the vaccinated mice increased with time after vaccination. The titers of anti-HBs in the rCHO vaccine group at day 7 were similar to the rSC vaccine group, but significantly higher than that of the rHP vaccine group (P = 0.044 < 0.05). The anti-HBs titers of the rCHO vaccine group at day 14 were significantly higher as compared to the rSC (P = 0.012 < 0.05) and rHP (P = 0.009 < 0.05) vaccine groups.
The immune responses induced by the three kinds of rHB vaccines were different in their patterns and levels. According to the intensity of early cellular immune response, the two yeast HB vaccines were superior to the rCHO vaccine, especially to the rHP vaccine. In contrast, the rCHO vaccine induced early seroconversion and high levels of anti-HBs.
评估免疫小鼠对不同种类重组乙型肝炎(rHB)疫苗的细胞免疫和体液免疫反应的动态变化。
在一系列时间点,用HBsAg MHC I类肽S28 - 39或HBsAg体外刺激接种疫苗小鼠的脾单核细胞(MNC)后,采用酶联免疫斑点法(ELISPOT)检测IFN-γ和IL-2的分泌水平。通过特异性裂解试验检测免疫小鼠的淋巴细胞毒性(CTL),并用雅培IMX试剂盒检测抗-HBs水平。
ELISPOT检测到接种疫苗小鼠中IFN-γ和IL-2的峰值出现在免疫后10 - 14天。源自酵母细胞(多形汉逊酵母)的rHB疫苗(rHP疫苗)诱导的CTL和IFN-γ水平显著高于其他两种疫苗(P < 0.05)。CTL的最大裂解出现在免疫后第10天的接种疫苗小鼠中,百分比为39.8%。rHP疫苗诱导的IL-2水平显著高于其他两种疫苗(P < 0.05)。然而,免疫后第7天和第14天,rSC(酿酒酵母)疫苗组的IL-2水平高于rCHO疫苗组(7天t = 4.595,P = 0.001 < 0.05;14天t = 5.721,P = 0.000 < 0.05)。免疫后第7天,对rHP疫苗的细胞免疫反应最强,而对rCHO疫苗的反应最弱。接种疫苗小鼠中抗-HBs的血清阳性率和滴度随接种后时间增加。rCHO疫苗组第7天的抗-HBs滴度与rSC疫苗组相似,但显著高于rHP疫苗组(P = 0.044 < 0.05)。rCHO疫苗组第14天的抗-HBs滴度显著高于rSC(P = 0.012 < 0.05)和rHP(P = 0.009 < 0.05)疫苗组。
三种rHB疫苗诱导的免疫反应在模式和水平上有所不同。根据早期细胞免疫反应强度,两种酵母乙型肝炎疫苗优于rCHO疫苗,尤其是rHP疫苗。相比之下,rCHO疫苗诱导早期血清转化和高水平的抗-HBs。