Optimization of non-coding regions for a non-modified mRNA COVID-19 vaccine.
Optimization of non-coding regions for a non-modified mRNA COVID-19 vaccine.
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DOI：
10.1038/s41586-021-04231-6
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发表时间：
2022-01
期刊：
影响因子：
64.8
通讯作者：
Barouch DH
中科院分区：
文献类型：
--
作者：
Gebre MS;Rauch S;Roth N;Yu J;Chandrashekar A;Mercado NB;He X;Liu J;McMahan K;Martinot A;Martinez DR;Giffin V;Hope D;Patel S;Sellers D;Sanborn O;Barrett J;Liu X;Cole AC;Pessaint L;Valentin D;Flinchbaugh Z;Yalley-Ogunro J;Muench J;Brown R;Cook A;Teow E;Andersen H;Lewis MG;Boon ACM;Baric RS;Mueller SO;Petsch B;Barouch DH
最近，在人类2b/3期疗效试验中评估了针对严重急性呼吸综合征冠状病毒-2（SARS-CoV-2）的CVnCoV（CureVac）mRNA疫苗。CV 2CoV是第二代mRNA疫苗，含有非修饰的核苷，但具有优化的非编码区和增强的抗原表达。在这里，我们报告了非人灵长类动物中CVnCoV和CV 2CoV的免疫原性和保护效力的头对头比较结果。我们用两个剂量的12 μg脂质纳米颗粒配制的CVnCoV或CV 2CoV或用假手术免疫18只食蟹猴（每组n = 6）。与CVnCoV相比，CV 2CoV诱导的结合和中和抗体滴度、记忆B细胞应答和T细胞应答显著更高，并且针对SARS-CoV-2变体（包括Delta变体）的中和抗体应答更强。此外，发现CV 2CoV在猕猴中对BNT 162 b2（Pfizer）疫苗具有免疫原性。尽管CVnCoV对SARS-CoV-2攻击提供了部分保护，但CV 2CoV在上呼吸道和下呼吸道中具有显著较低的病毒载量，提供了更强的保护。结合和中和抗体滴度与保护效力相关。这些数据表明，非编码区的优化可以大大提高非修饰mRNA SARS-CoV-2疫苗在非人灵长类动物中的免疫原性和保护效力。CV 2CoV是一种第二代mRNA COVID-19疫苗，具有未修饰的核苷，但优化了非编码区，在非人灵长类动物中进行测试时，证明可有效对抗SARS-CoV-2攻击。
The CVnCoV (CureVac) mRNA vaccine for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) was recently evaluated in a phase 2b/3 efficacy trial in humans. CV2CoV is a second-generation mRNA vaccine containing non-modified nucleosides but with optimized non-coding regions and enhanced antigen expression. Here we report the results of a head-to-head comparison of the immunogenicity and protective efficacy of CVnCoV and CV2CoV in non-human primates. We immunized 18 cynomolgus macaques with two doses of 12 μg lipid nanoparticle-formulated CVnCoV or CV2CoV or with sham (n = 6 per group). Compared with CVnCoV, CV2CoV induced substantially higher titres of binding and neutralizing antibodies, memory B cell responses and T cell responses as well as more potent neutralizing antibody responses against SARS-CoV-2 variants, including the Delta variant. Moreover, CV2CoV was found to be comparably immunogenic to the BNT162b2 (Pfizer) vaccine in macaques. Although CVnCoV provided partial protection against SARS-CoV-2 challenge, CV2CoV afforded more robust protection with markedly lower viral loads in the upper and lower respiratory tracts. Binding and neutralizing antibody titres were correlated with protective efficacy. These data demonstrate that optimization of non-coding regions can greatly improve the immunogenicity and protective efficacy of a non-modified mRNA SARS-CoV-2 vaccine in non-human primates. CV2CoV, a second-generation mRNA COVID-19 vaccine with non-modified nucleosides but optimized non-coding regions, is demonstrated to be effective against SARS-CoV-2 challenge when tested in non-human primates.
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BNT162B2 mRNA COVID-19疫苗的安全性和功效。
DOI：
10.1056/nejmoa2034577
发表时间：
2020-12-31
期刊：
The New England journal of medicine
影响因子：
--
作者：
Polack FP;Thomas SJ;Kitchin N;Absalon J;Gurtman A;Lockhart S;Perez JL;Pérez Marc G;Moreira ED;Zerbini C;Bailey R;Swanson KA;Roychoudhury S;Koury K;Li P;Kalina WV;Cooper D;Frenck RW Jr;Hammitt LL;Türeci Ö;Nell H;Schaefer A;Ünal S;Tresnan DB;Mather S;Dormitzer PR;Şahin U;Jansen KU;Gruber WC;C4591001 Clinical Trial Group
通讯作者：
C4591001 Clinical Trial Group
影响因子：
7.3
作者：
Lafon E;Diem G;Witting C;Zaderer V;Bellmann-Weiler RM;Reindl M;Bauer A;Griesmacher A;Fux V;Hoermann G;Miller C;Zabernigg A;Wöll E;Wilflingseder D;Lass-Flörl C;Posch W
通讯作者：
Posch W
影响因子：
9.2
作者：
Lutz J;Lazzaro S;Habbeddine M;Schmidt KE;Baumhof P;Mui BL;Tam YK;Madden TD;Hope MJ;Heidenreich R;Fotin-Mleczek M
通讯作者：
Fotin-Mleczek M
影响因子：
64.5
作者：
Liu C;Ginn HM;Dejnirattisai W;Supasa P;Wang B;Tuekprakhon A;Nutalai R;Zhou D;Mentzer AJ;Zhao Y;Duyvesteyn HME;López-Camacho C;Slon-Campos J;Walter TS;Skelly D;Johnson SA;Ritter TG;Mason C;Costa Clemens SA;Gomes Naveca F;Nascimento V;Nascimento F;Fernandes da Costa C;Resende PC;Pauvolid-Correa A;Siqueira MM;Dold C;Temperton N;Dong T;Pollard AJ;Knight JC;Crook D;Lambe T;Clutterbuck E;Bibi S;Flaxman A;Bittaye M;Belij-Rammerstorfer S;Gilbert SC;Malik T;Carroll MW;Klenerman P;Barnes E;Dunachie SJ;Baillie V;Serafin N;Ditse Z;Da Silva K;Paterson NG;Williams MA;Hall DR;Madhi S;Nunes MC;Goulder P;Fry EE;Mongkolsapaya J;Ren J;Stuart DI;Screaton GR
通讯作者：
Screaton GR
影响因子：
5.4
作者：
Dagotto, Gabriel;Mercado, Noe B.;Barouch, Dan H.
通讯作者：
Barouch, Dan H.