被动免疫轮状病毒NSP4&VP7双抗原重组腺病毒对感染乳鼠的排毒保护作用  

Passive Immune Protection of Recombinant Adenovirus Expressing Rotavirus NSP4&VP7 in Neonatal Mice

作　　者：谢力 曾韦锟 贾静 句红萍 唐丽媛 秦林才 吴晋元 李鸿钧 孙茂盛 XIE Li;ZENG Weikun;JIA Jing;JU Hongping;TANG Liyuan;QIN Lincai;WU Jinyuan;LI Hongjun;SUN Maosheng(Medical School of Kunming University,Kunming 650214,China;Institute of Medical Biology,Chinese Academy of Medical Sciences/Peking Union Medical College,Yunnan Key Laboratory of Vaccine Research and Development on Severe Infectious Diseases,Kunming 650118,China)

机构地区：[1]昆明学院医学院,昆明650214 [2]中国医学科学院医学生物学研究所,北京协和医学院,云南省重大传染病疫苗研发重点实验室,昆明650214

出　　处：《病毒学报》2021年第6期1341-1347,共7页Chinese Journal of Virology

基　　金：国家自然科学基金项目(项目号:81760304),题目:轮状病毒NSP4蛋白的粘膜佐剂效应及分子机制研究;云南省教育厅科研项目(项目号:2017ZZX092),题目:携带基因佐剂的HPV E7DNA疫苗所诱导的免疫应答与抗肿瘤效应研究;云南省科技厅高校联合重点项目(项目号:2018FH001-005),题目:甲型副伤寒杆菌新型减毒疫苗的构建及免疫保护性研究。

摘　　要：为建立小鼠轮状病毒(Rotavirus,RV)感染动物模型,研究可同时表达轮状病毒NSP4(Nonstructural protein4)和VP7(Viral protein 7)的重组腺病毒疫苗免疫孕鼠后对新生乳鼠感染RV的被动保护作用。新生乳鼠口服异源株轮状病毒Wa、ZTR-68或SA11株后(分2次给予,每次含5×10^(4)CCID_(50)的RV),观察乳鼠是否有腹泻症状、肠道病理变化,检测乳鼠粪便排毒百分率;另以重组腺病毒rAd-NSP4-VP7免疫孕鼠后,检测母鼠血清抗体产生情况,并对比乳鼠粪便中RV抗原检出率初步评价疫苗的被动免疫保护作用。发现口服异源株RV的乳鼠未出现类似人类婴幼儿感染后的明显腹泻症状,但在粪便中可检测到RV抗原的存在(Wa、ZTR-68攻毒组均超过80%)。经rAd-NSP4-VP7被动免疫的乳鼠接受Wa和ZTR-68攻毒后其粪便中的RV检出率比未受到被动免疫保护的对照组降低(P<0.05)。rAd-NSP4-VP7重组腺病毒免疫母鼠可显示出对孕鼠感染RV的被动免疫保护作用。To model rotavirus(RV)- infected neonatal mice,and investigate the passive immune protective efficacy of the recombinant adenovirus expressing NSP4 and VP7 antigens against RV infection. Neonatal mice were challenged with a heterologous rotavirus Wa,ZTR-68,or SA11 strain(5×10^(4) CCID_(50) RV in 50 μL)via oral route. Diarrhea score,morphologic observation in jejunum and percentage of RV fecal shedding were assessed. After the pregnant mice were immunized with the recombinant adenovirus(rAd - NSP4 - VP7),the serum antibody titers in mother mice were analyzed and the vaccine efficacy in neonatal mice was measured as the percentage reduction of RV fecal shedding. Severe diarrhea was not observed in neonatal mice after heterologous RV infection. However,RV antigens in feces were detected in most neonatal mice(>80% in Wa or ZTR - 68 challenged groups). Furthermore,a significant reduction in shedding percentage was observed in vaccine passive immunization groups after challenge with ZTR-68 or Wa(P < 0.05).In neonatal mice,passive immune protection against RV infection was confirmed by the reduction of shedding percentage after the pregnant mice was immunized with rAd-NSP4-VP7.

关 键 词：轮状病毒(RV) NSP4 VP7 重组腺病毒 乳鼠 被动免疫 

分 类 号：R373.2[医药卫生—病原生物学]