SARS-CoV-2 Beta变异株和甲型流感病毒H3N2双价重组腺病毒载体疫苗可在小鼠诱导免疫保护  

A Novel Bivalent Recombinant Adenovirus Vector Vaccine Induces Immune Protection in Mice Against SARS-CoV-2 Beta Variant and Influenza A Virus H3N2

作　　者：韩頔 郭小娟[2] 翟程程 邓瑶[2] 黄保英[2] 胡月超 任皎[2] 王文[2] 郭俊佳 鲁福娜 王文玲[2] 沈晓玲 鲁茁壮[2] 王君 谭文杰[2] HAN Di;GUO Xiaojuan;ZHAI Chengcheng;DENG Yao;HUANG Baoying;HU Yuechao;REN Jiao;WANG Wen;GUO Junjia;LU Funa;WANG Wenling;SHEN Xiaoling;LU Zhuozhuang;WANG Jun;TAN Wenjie(Basic Medical College,Inner Mongolia Medical University,Hohhot 010110;National Health Commission(NHC)Key Laboratory of Biosafety,National Institute for Viral Disease Control and Prevention,Beijing 102206;School of Public Health,Inner Mongolia Baotou Medical College,Baotou,014000;School of Laboratory Medicine and Life Sciences,Wenzhou Medical University,Wenzhou 325035)

机构地区：[1]内蒙古医科大学基础医学院,呼和浩特010110 [2]中国疾病预防控制中心病毒病预防控制所卫健委生物安全重点实验室,北京102206 [3]内蒙古科技大学包头医学院公共卫生学院,包头014000 [4]温州医科大学检验医学院生命科学学院,温州325035

出　　处：《病毒学报》2022年第5期1025-1034,共10页Chinese Journal of Virology

基　　金：国家自然科学基金(国际合作与交流项目)(项目号:82161138001),题目:基于肠道腺病毒载体平台COVID-19粘膜疫苗的设计与筛选;国家自然科学基金(项目号:82041041),题目:自然感染和疫苗接种人群中的广谱保护性免疫应答规律;国家重点研发计划(项目号:2021YFC0863300),题目:新型冠状病毒变异监测及功能影响分析。

摘　　要：评价一种SARS-CoV-2 Beta变异株和甲型流感病毒H3N2新型重组双价疫苗在小鼠模型中的免疫保护效果。本研究构建了表达SARS-CoV-2南非变异株(B.1.351)棘突蛋白1(S1)和H3N2柬埔寨分离株(A/Cambodia/e0826360/2020)血凝素(HA)的重组双价非复制Ad5载体疫苗,命名为HAdV5-S1-2A-HA,经单针肌肉注射免疫BALB/c雌鼠后,采用ELISA、血凝抑制实验、假病毒中和实验与Elispot实验进行体液与细胞免疫学检测,免后3~6周采用H3N2-X31病毒、H1N1-PR8与SARS-CoV-2(B.1.351)进行攻毒保护实验。HAdV5-S1-2A-HA免疫两周后,低剂量组(1×10^(8)vp/只)免疫小鼠后可检出HA特异体液免疫与S1特异的细胞免疫应答;而高剂量组(5×10^(9)vp/只)诱导小鼠产生了较强的双抗原(S1,HA)特异的体液和细胞免疫应答,并能完全保护小鼠对H3N2-X31攻击,降低SARS-CoV-2(B.1.351)感染后小鼠肺部病毒载量,延迟H1N1-PR8病毒感染后小鼠死亡发生。本研究制备的重组双价疫苗HAdV5-S1-2A-HA在小鼠体内诱导抗原特异的体液与细胞免疫应答。同时,它还可以在小鼠中诱导对SARS-CoV-2和H3N2感染的免疫保护,具有较好的研发与应用前景。To evaluate the immunological protective effect of a novel recombinant bivalent vaccine against SARS-CoV-2 Beta variant and influenza A virus H3N2 in a mouse model.We construct an adenovirus 5(Ad5)-based bivalent vaccines designed to Spike 1(S1)from SARS-CoV-2(B.1.351)and hemagglutinin(HA)from the H3N2 Cambodia strain(A/Cambodia/e0826360/2020),which we named“HAdV5-S1-2A-HA”.ELISA,hemagglutination inhibition test,pseudovirus neutralization test and Elispot assay were used for detection of humoral and cellular immunological responses in BALB/c female mice after a single immunization by intramuscular injection.Then challenge protections against H3N2-X31,H1N1-PR8 and SARS-CoV-2(B.1.351)were performed in mice 3-6weeks post immunization.Two weeks after HAdV5-S1-2A-HA immunization,HA-specific humoral immunity and S1-specific cellular immune responses could be detected in the low-dose group(1×10^(8)vp/mouse),while the high-dose group(5×10^(9)vp/mouse)induced robust dual-antigen(S1,HA)-specific humoral and cellular immune responses,and could protect mice completely against H3N2-X31 challenge and extenuate SARS-CoV-2(B.1.351)infection based on reduction of the viral load in mouse lungs,delayed death occurs in immunized mice with high dose of HAdV5-S1-2A-HA after H1N1-PR8virus infection.The recombinant bivalent vaccine HAdV5-S1-2A-HA developed in this study induced antigenspecific humoral and cellular immune responses in mice.Furthermore it also induced immune protection against SARS-CoV-2 and H3N2 infection in mice,which has good application prospects for further research and development.

关 键 词：新型冠状病毒 流感病毒 腺病毒载体 疫苗 棘突蛋白1 血凝素 免疫保护 

分 类 号：R373.1[医药卫生—病原生物学]