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Rapid evaluation of heterologous chimeric RBD-dimer mRNA vaccine for currently-epidemic Omicron sub-variants as booster shot after inactivated vaccine 被引量:1
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作者 Qian Chen Pei Du +14 位作者 Yuxuan Han Xuehui Ma rong Zhang xiaoyu rong Xu Zhao Renyi Ma Huiting Yang Anqi Zheng Qingrui Huang Jinghua Yan Hui Wang Xin Zhao Lianpan Dai George F.Gao Qihui Wang 《Biosafety and Health》 CAS CSCD 2023年第2期89-100,共12页
With continuous mutations of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),the severe immune escape of Omicron sub-variants urges the development of next-generation broad-spectrum vaccines,especially as ... With continuous mutations of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),the severe immune escape of Omicron sub-variants urges the development of next-generation broad-spectrum vaccines,especially as booster jabs after high-level vaccination coverage of inactivated vaccines in China and many other countries.Previously,we developed a coronavirus disease 2019(COVID-19)protein subunit vaccine ZF2001?based on the tandem homo-prototype receptor-binding domain(RBD)-dimer of the SARS-CoV-2 spike protein.We upgraded the antigen into a hetero-chimeric prototype(PT)-Beta or Delta-BA.1 RBD-dimer to broaden the cross-protection efficacy and prove its efficiency with protein subunit and mRNA vaccine platforms.Herein,we further explored the hetero-chimeric RBD-dimer mRNA vaccines and evaluated their broad-spectrum activities as booster jabs following two doses of inactivated vaccine(Ⅳ)in mice.Our data demonstrated that the chi-meric vaccines significantly boosted neutralizing antibody levels and specific T-cell responses against the vari-ants,and PT-Beta was superior to Delta-BA.1 RBD as a booster in mice,shedding light on the antigen design for the next-generation COVID-19 vaccines. 展开更多
关键词 SARS-CoV-2 RBD-dimer mRNA Vaccine BROAD-SPECTRUM Omicron BA.5
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新冠病毒变异株RBD二聚体mRNA疫苗广谱免疫原性研究
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作者 赵旭 吴鑫凯 +16 位作者 杜沛 陈茜 马雪慧 胡世雄 吴春丽 杨惠婷 马任义 李爽 孔天翔 李睿琦 冯英浩 王晓云 荣笑雨 郑安琪 陆剑 高福 王奇慧 《科学通报》 EI CAS 2024年第33期4905-4916,共12页
严重急性呼吸综合征冠状病毒2(severe acute respiratory syndrome coronavirus 2,SARS-CoV-2)是导致新冠病毒病(coronavirus disease 2019,COVID-19)的病原体.2019年末至今,SARS-CoV-2在全球范围流行,氨基酸突变累积产生多种具有较高... 严重急性呼吸综合征冠状病毒2(severe acute respiratory syndrome coronavirus 2,SARS-CoV-2)是导致新冠病毒病(coronavirus disease 2019,COVID-19)的病原体.2019年末至今,SARS-CoV-2在全球范围流行,氨基酸突变累积产生多种具有较高传播力或较强免疫逃逸能力的变异株.目前广泛使用的COVID-19疫苗大多基于SARS-CoV-2原型株(prototype,PT)进行免疫原设计.这些疫苗针对早期变异株具有较好的保护效果,然而面对后续出现的Omicron系列变异株,以原型株为免疫原的疫苗保护效力显著下降,特别是在面对免疫逃逸极强的BF.7、BQ.1.1、CH.1.1、XBB及XBB.1.5等变异株时,难以激发较高水平特异性中和抗体.因此,亟须研发针对多种SARS-CoV-2变异株产生高效中和抗体的新一代广谱疫苗.本研究基于SARS-CoV-2受体结合域(receptor-binding domain,RBD)重复串联二聚体的构型,设计了6种包含Delta RBD以及BA.1、BA.2和BA.5等Omicron亚型RBD的串联二聚体mRNA疫苗,并对其表达情况及免疫原性进行了系统性评价.同时,还验证了在两针灭活疫苗基础上以mRNA疫苗作为加强针的序贯免疫效果.假病毒中和数据显示,Delta-BA.2(DO2)与Delta-BA.5(DO5)RBD二聚体疫苗表现出较优的免疫原性,且两者诱导的中和抗体分别针对BA.2之前和BA.5之后出现的变异株有较好的中和活性,表现出一定的互补趋势.因此,我们设计了DO2和DO5混合免疫的策略,实现了对二者优势的互补,进一步扩宽了疫苗中和抗体谱.在三剂免疫的结果中,DO5及DO2+DO5免疫可产生针对CH.1.1、XBB及XBB.1.5的高水平中和抗体.这些结果有助于我们理解不同分支变异株中和抗体谱的变化规律,并为广谱COVID-19疫苗设计提供了参考. 展开更多
关键词 SARS-CoV-2 Omicron变异株 mRNA疫苗 广谱疫苗
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