摘要
目的 探索绝经后雌激素水平下降对狂犬疫苗免疫效果的影响。方法 通过卵巢切除术(OVX)建立雌激素缺乏小鼠模型,术后2周检测小鼠的雌激素水平和子宫重量验证模型。将狂犬病毒株LBNSE株免疫OVX小鼠和正常小鼠,连续观察21 d临床指征,评估疫苗的安全性。通过FVAN试验测定免疫后2、4、8周时中和抗体水平,并使用ELISA测定血清中狂犬病毒特异性IgG1与IgG2a抗体亚型的比例;采用流式细胞术检测小鼠淋巴结中B细胞和树突状细胞(DC)募集/活化情况。结果 卵巢切除后小鼠雌激素水平和子宫重量显著低于对照组,表明成功构建雌激素缺乏小鼠模型;接种疫苗后,OVX小鼠未出现明显临床症状,并在攻毒保护实验中全部存活;4周和8周的中和抗体水平低于对照组,但高于有效保护水平0.5 IU/mL可100%保护小鼠;IgG1与IgG2a抗体亚型的比例显示,OVX小鼠偏向Th2型免疫应答;在早期免疫反应阶段,OVX小鼠淋巴结募集和活化的CD19CD40 B细胞和CD86CD11c Dc细胞的比例上升与下降速度快于对照组。结论 雌激素缺乏小鼠接种狂犬疫苗后无不良反应,抗体水平虽低于对照组,但能够保护病毒攻击。本研究为绝经期女性接种狂犬疫苗免疫效果提供相关的理论依据,有助于缓解绝经期妇女暴露于狂犬病毒时的恐慌焦虑。
Objective To investigate whether immune alterations due to estrogen deficiency in postmenopausal women affect infection protection after rabies vaccination.Methods Female BALB/c mice aged 8-10 weeks were randomized into LBNSE-OVX,LBNSE and Mock groups.The LBNSE-OVX group underwent bilateral ovariectomy,while sham surgery was carried out in the LBNSE group,both of which were immunized with recombinant RABV LBNSE.Then,the pathogenicity of LBNSE in the three groups were monitored.After immunization,the titers of rabies virus neutralizing antibodies were measured by the fluorescent antibody virus neutralization assay(FVAN)and the levels of IgGland IgG2a antibodies against RABV were determined by the Enzyme linked immunosorbent assay(Elisa)The proportions of activated dendritic cells or B cells in the lymph nodes of three groups were detected by flow cytometry.ResultsTThe serum estrogen levels and uterine weights of the OVX mice were significantly lower than those underwent sham sugery.All the three groups mice showed no abnormal behaviour or neurological signs during the observation period.The average titers of neutralizing antibodies in the LBNSE-OVX group were slightly lower(p>0.05)than LBNSE group at 4 weeks,but still showed 1oo%protection against RABV.Moreover,the LBNSE mice exhibited more even Thl-and Th2-type immune responses,while LBNSE-OVX mice tended to exhibit Th2-dominant humoral immune responses in the later stage of immunity.The percentage of CD19+CD40+B cells and CD86+CD11c+DCs in the lymph nodes of the LBNSE-OVX group grew and declined at a rapider rate than that of the other two groups.Conclusion In this study,our data illustrated that the protective efficacy of rabies vaccination was slightly decreased by estrogen deficiency,but it offered sufficient protection against RABV,helping alleviate fears and anxieties related to rabies virus exposure during menopause.
作者
张军杰
钱华
田莉
吴鑫宇
刘乐乐
蒋玉芬
徐琳乐
李梦华
郑文文
郑学星
ZHANG Junjie;QIAN Hua;TIAN Li;WU Xinyu;LIU Lele;JIANG Yufen;XU Linyue;LI Menghua;ZHENG Wenwen;ZHENG Xuexing(School of public health,Cheeloo Collage Medicine,Shandong University,Jinan 250012,China;Center of Stomatology,the Second Hospital of Shandong University)
出处
《中国病原生物学杂志》
CSCD
北大核心
2024年第12期1425-1430,共6页
Journal of Pathogen Biology
基金
国家重点研发计划项目(No.2022YFC2305005)
国家自然科学基金项目(No.82272335)
山东省自然科学基金项目(No.ZR2021MC010,ZR2021QH140)
济南市临床医学科技创新计划项目(No.202328045)
山东省口腔组织再生重点实验室开放课题(No.SDDX202103)。
关键词
狂犬病疫苗
中和抗体
卵巢切除
绝经期
rabies vaccine
neutralizing antibodies
ovariectomy
menopause
作者简介
张军杰(1999-),男,安徽人,硕士研究生,主要从事分子病毒学研究,E-mail:1755698549@qq.com;通讯作者:郑学星,E-mail:zhengxuexing@sdu.edu.cn。
