Multiplexed LNP-mRNA vaccination against pathogenic coronavirus species.
Multiplexed LNP-mRNA vaccination against pathogenic coronavirus species.
复制标题
针对致病性冠状病毒物种的多重LNP-mRNA疫苗接种。
DOI：
10.1016/j.celrep.2022.111160
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发表时间：
2022-08-02
期刊：
影响因子：
8.8
通讯作者：
Chen, Sidi
中科院分区：
文献类型：
--
作者：
Peng, Lei;Fang, Zhenhao;Renauer, Paul A.;McNamara, Andrew;Park, Jonathan J.;Lin, Qianqian;Zhou, Xiaoyu;Dong, Matthew B.;Zhu, Biqing;Zhao, Hongyu;Wilen, Craig B.;Chen, Sidi
虽然已经研制出新型冠状病毒疫苗，但存在多致病性冠状病毒，迫切需要研制多种冠状病毒疫苗。在这里，我们开发了针对SARS-CoV-2 Delta、SARS-CoV和MERS-CoV的脂质纳米颗粒（LNP） mrna候选疫苗的原型，并在动物模型中测试了LNP-mRNA多重组合如何诱导有效的免疫反应。三联和双联LNP-mRNA疫苗接种可诱导针对SARS-CoV-2、SARS-CoV和MERS-CoV的抗原特异性抗体反应。单细胞RNA测序分析了接种疫苗动物的整体系统免疫谱和各自的转录组特征，揭示了激活B细胞的全身性增加和主要适应性免疫细胞的差异基因表达。顺序接种显示对所有三种物种的有效抗体反应，明显强于同时接种混合疫苗。这些数据证明了多物种冠状病毒疫苗接种的可行性、抗体应答和单细胞免疫谱。同时接种疫苗和顺序接种疫苗之间的直接比较为优化接种计划提供了见解，以提供针对三种主要致病性冠状病毒物种的广泛和有效的抗体免疫。Peng等人证明了针对三种主要致病性冠状病毒（SARS-CoV-2、SARS-CoV和MERS-CoV）的mRNA候选疫苗的有效性，并发现疫苗接种时间表和抗原免疫原性影响抗体反应的程度。单细胞分析揭示了与针对这些冠状病毒的多路mRNA疫苗接种相关的免疫群体和转录组学变化。
Although COVID-19 vaccines have been developed, multiple pathogenic coronavirus species exist, urging on development of multispecies coronavirus vaccines. Here we develop prototype lipid nanoparticle (LNP)-mRNA vaccine candidates against SARS-CoV-2 Delta, SARS-CoV, and MERS-CoV, and we test how multiplexing LNP-mRNAs can induce effective immune responses in animal models. Triplex and duplex LNP-mRNA vaccinations induce antigen-specific antibody responses against SARS-CoV-2, SARS-CoV, and MERS-CoV. Single-cell RNA sequencing profiles the global systemic immune repertoires and respective transcriptome signatures of vaccinated animals, revealing a systemic increase in activated B cells and differential gene expression across major adaptive immune cells. Sequential vaccination shows potent antibody responses against all three species, significantly stronger than simultaneous vaccination in mixture. These data demonstrate the feasibility, antibody responses, and single-cell immune profiles of multispecies coronavirus vaccination. The direct comparison between simultaneous and sequential vaccination offers insights into optimization of vaccination schedules to provide broad and potent antibody immunity against three major pathogenic coronavirus species. Peng et al. demonstrate the efficacy of mRNA vaccine candidates targeting three major pathogenic coronavirus species (SARS-CoV-2, SARS-CoV, and MERS-CoV) and find that vaccination schedules and antigen immunogenicity influence the magnitude of antibody responses. Single-cell profiling reveals immune population and transcriptomics changes associated with multiplexed mRNA vaccination against these coronaviruses.
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影响因子：
14.9
作者：
Goujon M;McWilliam H;Li W;Valentin F;Squizzato S;Paern J;Lopez R
通讯作者：
Lopez R
DOI：
10.1126/science.abm0620
发表时间：
2022-01-21
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
通讯作者：
--
影响因子：
56.9
作者：
Hsieh, Ching-Lin;Goldsmith, Jory A.;McLellan, Jason S.
通讯作者：
McLellan, Jason S.
DOI：
10.1056/nejmoa2109072
发表时间：
2021-10-14
期刊：
The New England journal of medicine
影响因子：
--
作者：
Bergwerk M;Gonen T;Lustig Y;Amit S;Lipsitch M;Cohen C;Mandelboim M;Levin EG;Rubin C;Indenbaum V;Tal I;Zavitan M;Zuckerman N;Bar-Chaim A;Kreiss Y;Regev-Yochay G
通讯作者：
Regev-Yochay G
DOI：
10.1056/nejmoa2035389
发表时间：
2021-02-04
期刊：
The New England journal of medicine
影响因子：
--
作者：
Baden LR;El Sahly HM;Essink B;Kotloff K;Frey S;Novak R;Diemert D;Spector SA;Rouphael N;Creech CB;McGettigan J;Khetan S;Segall N;Solis J;Brosz A;Fierro C;Schwartz H;Neuzil K;Corey L;Gilbert P;Janes H;Follmann D;Marovich M;Mascola J;Polakowski L;Ledgerwood J;Graham BS;Bennett H;Pajon R;Knightly C;Leav B;Deng W;Zhou H;Han S;Ivarsson M;Miller J;Zaks T;COVE Study Group
通讯作者：
COVE Study Group