RBD-mRNA vaccine induces broadly neutralizing antibodies against Omicron and multiple other variants and protects mice from SARS-CoV-2 challenge.
RBD-mRNA vaccine induces broadly neutralizing antibodies against Omicron and multiple other variants and protects mice from SARS-CoV-2 challenge.
复制标题
RBD-MRNA疫苗可诱导针对Omicron和其他多种变体的广泛中和抗体，并保护小鼠免受SARS-COV-2挑战。
DOI：
10.1016/j.trsl.2022.04.007
复制
发表时间：
2022-10
期刊：
影响因子：
--
通讯作者：
Du L
中科院分区：
文献类型：
--
作者：
Shi J;Zheng J;Zhang X;Tai W;Odle AE;Perlman S;Du L
发现多种SARS-CoV-2变体具有较高的传播率或更严重的疾病严重程度。特别是，最近出现的具有快速人际传播的欧米克隆变异对当前的预防策略提出了新的挑战。在本研究中，在接种编码SARS-CoV-2受体结合域（RBD-mRNA）的mRNA疫苗后，我们检测了血清抗体，这些抗体可以中和表达含有单个或多个突变的刺突(S)蛋白的假病毒，以及真正的SARS-CoV-2变体，并评估其对SARS-CoV-2感染的保护作用。该疫苗诱导的持久抗体能有效中和含有N501Y或D614G突变的原型株和B.1.1.7谱系变异假病毒，或与N439K突变（B.1.258谱系）、L452R突变（B.1.427或B.1.429谱系）或L452R- e484q双突变（B.1.617.1变体）的假病毒，尽管对含有S蛋白10个氨基酸变化的B.1.1.7谱系变异的中和活性略有降低。rdb - mrna诱导的抗体对真实的B.1.617.2和B.1.1.529变体、含有K417N/T、E484K和N501Y突变的伪型B.1.351和P.1谱系变体、含有L452R、T478K和P681R突变的B.1.617.2谱系变体和含有38个S蛋白突变的B.1.1.529谱系变体具有中等中和作用。特别是，RBD-mRNA疫苗完全保护小鼠免受小鼠适应性强毒SARS-CoV-2变体的攻击。其中，B.1.1.7、B.1.351、P.1、B.1.617.2和B.1.1.529分别属于Alpha、Beta、Gamma、Delta和Omicron变体。我们的观察结果表明，RBD-mRNA疫苗是有希望的，并强调需要设计具有更好中和性的新型疫苗，以对抗当前和未来的大流行SARS-CoV-2变体。
Multiple SARS-CoV-2 variants are identified with higher rates of transmissibility or greater disease severity. Particularly, recent emergence of Omicron variant with rapid human-to-human transmission posts new challenges to the current prevention strategies. In this study, following vaccination with an mRNA vaccine encoding SARS-CoV-2 receptor-binding domain (RBD-mRNA), we detected serum antibodies that neutralized pseudoviruses expressing spike (S) protein harboring single or multiple mutations, as well as authentic SARS-CoV-2 variants, and evaluated its protection against SARS-CoV-2 infection. The vaccine induced durable antibodies that potently neutralized prototypic strain and B.1.1.7 lineage variant pseudoviruses containing N501Y or D614G mutations alone or in combination with a N439K mutation (B.1.258 lineage), with a L452R mutation (B.1.427 or B.1.429 lineage), or a L452R-E484Q double mutation (B.1.617.1 variant), although neutralizing activity against B.1.1.7 lineage variant containing 10 amino acid changes in the S protein was slightly reduced. The RBD-mRNA-induced antibodies exerted moderate neutralization against authentic B.1.617.2 and B.1.1.529 variants, and pseudotyped B.1.351 and P.1 lineage variants containing K417N/T, E484K, and N501Y mutations, the B.1.617.2 lineage variant harboring L452R, T478K, and P681R mutations, and the B.1.1.529 lineage variant containing 38 mutations in the S protein. Particularly, RBD-mRNA vaccine completely protected mice from challenge with a virulent mouse-adapted SARS-CoV-2 variant. Among these lineages, B.1.1.7, B.1.351, P.1, B.1.617.2, and B.1.1.529 belong to Alpha, Beta, Gamma, Delta, and Omicron variants, respectively. Our observations reveal that RBD-mRNA vaccine is promising and highlights the need to design novel vaccines with improved neutralization against current and future pandemic SARS-CoV-2 variants.
登录
查看更多内容
DOI：
10.1016/j.medj.2021.11.004
发表时间：
2021-12-10
期刊：
Med (New York, N.Y.)
影响因子：
--
作者：
Chen RE;Gorman MJ;Zhu DY;Carreño JM;Yuan D;VanBlargan LA;Burdess S;Lauffenburger DA;Kim W;Turner JS;Droit L;Handley SA;Chahin S;Deepak P;O'Halloran JA;Paley MA;Presti RM;Wu GF;Krammer F;Alter G;Ellebedy AH;Kim AHJ;Diamond MS
通讯作者：
Diamond MS
DOI：
10.1016/j.lanepe.2021.100252
发表时间：
2022-01
期刊：
The Lancet regional health. Europe
影响因子：
--
作者：
Allen H;Vusirikala A;Flannagan J;Twohig KA;Zaidi A;Chudasama D;Lamagni T;Groves N;Turner C;Rawlinson C;Lopez-Bernal J;Harris R;Charlett A;Dabrera G;Kall M;COVID-19 Genomics UK (COG-UK Consortium)
通讯作者：
COVID-19 Genomics UK (COG-UK Consortium)
影响因子：
24.1
作者：
Du L;Yang Y;Zhang X
通讯作者：
Zhang X
影响因子：
64.5
作者：
Hoffmann M;Arora P;Groß R;Seidel A;Hörnich BF;Hahn AS;Krüger N;Graichen L;Hofmann-Winkler H;Kempf A;Winkler MS;Schulz S;Jäck HM;Jahrsdörfer B;Schrezenmeier H;Müller M;Kleger A;Münch J;Pöhlmann S
通讯作者：
Pöhlmann S
影响因子：
64.8
作者：
Mlcochova P;Kemp SA;Dhar MS;Papa G;Meng B;Ferreira IATM;Datir R;Collier DA;Albecka A;Singh S;Pandey R;Brown J;Zhou J;Goonawardane N;Mishra S;Whittaker C;Mellan T;Marwal R;Datta M;Sengupta S;Ponnusamy K;Radhakrishnan VS;Abdullahi A;Charles O;Chattopadhyay P;Devi P;Caputo D;Peacock T;Wattal C;Goel N;Satwik A;Vaishya R;Agarwal M;Indian SARS-CoV-2 Genomics Consortium (INSACOG);Genotype to Phenotype Japan (G2P-Japan) Consortium;CITIID-NIHR BioResource COVID-19 Collaboration;Mavousian A;Lee JH;Bassi J;Silacci-Fegni C;Saliba C;Pinto D;Irie T;Yoshida I;Hamilton WL;Sato K;Bhatt S;Flaxman S;James LC;Corti D;Piccoli L;Barclay WS;Rakshit P;Agrawal A;Gupta RK
通讯作者：
Gupta RK