戊型肝炎病毒重组颗粒性蛋白疫苗在小鼠体内诱导的免疫应答研究

Immune Response Induced by Recombinant Particulate Hepatitis E Virus Vaccine in Mice

HEV 239是福建省医学分子病毒学研究中心实验室研制的一种戊型肝炎病毒(HEV)重组颗粒性蛋白疫苗,该文旨在研究HEV239蛋白疫苗在小鼠体内诱导产生特异性免疫应答的情况。将5μg HEV 239蛋白疫苗(239-Pro)、加铝佐剂疫苗(239-Vac)或加弗氏佐剂疫苗(239-CFA)肌肉注射免疫BALB/c鼠3次,第8周检测鼠血清抗HEV抗体及其亚类,同时用ELISPOT方法检测细胞毒性T细胞(CTL)应答。结果显示:239-Vac诱导的抗体滴度与239-CFA相当,高于无佐剂的239-Pro。239-Vac诱导的抗体中,IgG1/IgG2a比值显著高于239-CFA和239-Pro,主要为Th2型应答。除239-CFA之外,239-Vac和239-Pro也可诱导出一定的HEV抗原特异性I型Tc应答。提示:重组抗原HEV 239能诱导良好的抗体应答及一定的Tc1应答。

This paper evaluated the specific humoral and cellular immune responses induced by a recombinant particulate hepatitis E virus （HEV） vaccine （HEV 239） in BALB/c mice. Three groups, each of six BALB/c mice, were immunized with 5μg HEV 239 antigen （239-Pro）, antigen absorbed by alum adjuvant （239-Vac）, and antigen absorbed by complete Freund＇s adjuvant （239-CFA） respectively. Two weeks after three vaccinations at day 0, 28 and 42, level of anti-HEV IgG antibody and their sub-isotypes were determined. At the same time, spleen cells of vaccinated mice were separated and stimulated with P815 cells which had been infected with recombinant vaccinia virus WR-239（ containing the eDNA of HEV 239）. IFN-γ secreting CD8 ^＋ T cell frequencies were determined by ELISPOT assay. Results showed that geometric mean titer （GMT） of anti-HEV induced by 239-Vac was 1：28509, which was similar to that of 239-CFA vaccinated mice （ t = 0.35, P 〉 0.05）, and both were higher than that of 239-Pro vaccinated mice. The ratio of specific IgG1/IgG2a was 269.2 in 239-Vac group, which was higher than that of 239-CFA group （2.9） and 239-Pro group （11.7）. This result indicated that antibody induced by 239-Vac was more polarized to Th2. All the three vaccines induced HEV-specific CTL response, among which the CTL response in 239-CFA group was the strongest. The results suggested that recombinant 239 protein could induce good HEV-specific humoral immune response as well as Tel immune response in BALB/c mice.