COVAC1 phase 2a expanded safety and immunogenicity study of a self-amplifying RNA vaccine against SARS-CoV-2.
COVAC1 phase 2a expanded safety and immunogenicity study of a self-amplifying RNA vaccine against SARS-CoV-2.
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DOI：
10.1016/j.eclinm.2022.101823
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发表时间：
2023-02
影响因子：
15.1
通讯作者：
COVAC 1 Study Team
中科院分区：
文献类型：
--
作者：
Szubert AJ;Pollock KM;Cheeseman HM;Alagaratnam J;Bern H;Bird O;Boffito M;Byrne R;Cole T;Cosgrove CA;Faust SN;Fidler S;Galiza E;Hassanin H;Kalyan M;Libri V;McFarlane LR;Milinkovic A;O'Hara J;Owen DR;Owens D;Pacurar M;Rampling T;Skene S;Winston A;Woolley J;Yim YTN;Dunn DT;McCormack S;Shattock RJ;COVAC 1 Study Team
脂质纳米粒(LNP)包裹的自扩增RNA(SARNA)在18-75岁的SARS-CoV-2血清阴性和血清阳性个体中具有良好的耐受性和免疫原性。2020年8月10日至2021年7月30日，在英国的参与中心进行了SARNA SARS-CoV-2候选疫苗候选LNP-nCoVsaRNA的2a阶段扩大安全性和免疫原性研究。参与者接受1gμg和10gμg的LNP-nCoVsaRNA，∼相隔14周。在每次疫苗接种后一周内收集征求的不良事件(AEs)，并在整个过程中收集未征求的AEs。用S抗S蛋白免疫球蛋白夹心法和SARS-CoV-2假中和试验检测患者血清中抗SARS-CoV-2结合抗体和中和抗体。(试验注册：ISRCTN17072692，EudraCT2020-001646-20)。216名健康人(中位年龄51岁)接种了1.0gμg疫苗，随后接种了10.0gμg疫苗。已知有SARS-CoV2感染和(或)抗-Spike(S)抗体阳性的有28人。根据获得许可的新冠肺炎疫苗的反应，反应性与预期不谋而合，没有与疫苗接种有关的严重不良反应。80%的基线SARS-CoV-2幼稚个体(147/183)在第二次免疫后两周血清转换，无论年龄(18-75岁)；56%(102/183)有可检测到的中和抗体。几乎所有(28/31)SARS-CoV-2阳性个体在接种第一剂1.0gμ后，S免疫球蛋白结合抗体均升高，其中71%(22/31)的≥上升0.5log10。囊化SARNA在18-75岁的成年人中耐受性和免疫原性良好。在抗原NAIVE中的血清转换率高于我们在剂量范围研究中报道的结果。需要进一步的工作来确定这种差异是否与更长的剂量间隔(14对4周)有关，或者是先注射1.0gμg，然后再注射10.0gμg。在那些既有免疫应答的人中，单次注射1.0gμg可以观察到S抗体的增强。来自英国红十字会(MC_PC_19076)、/疫苗工作组、和的赠款和礼物。
Lipid nanoparticle (LNP) encapsulated self-amplifying RNA (saRNA) is well tolerated and immunogenic in SARS-CoV-2 seronegative and seropositive individuals aged 18–75. A phase 2a expanded safety and immunogenicity study of a saRNA SARS-CoV-2 vaccine candidate LNP-nCoVsaRNA, was conducted at participating centres in the UK between 10th August 2020 and 30th July 2021. Participants received 1 μg then 10 μg of LNP-nCoVsaRNA, ∼14 weeks apart. Solicited adverse events (AEs) were collected for one week post-each vaccine, and unsolicited AEs throughout. Binding and neutralisating anti-SARS-CoV-2 antibody raised in participant sera was measured by means of an anti-Spike (S) IgG ELISA, and SARS-CoV-2 pseudoneutralisation assay. (The trial is registered: ISRCTN17072692, EudraCT 2020-001646-20). 216 healthy individuals (median age 51 years) received 1.0 μg followed by 10.0 μg of the vaccine. 28/216 participants were either known to have previous SARS-CoV2 infection and/or were positive for anti-Spike (S) IgG at baseline. Reactogenicity was as expected based on the reactions following licensed COVID-19 vaccines, and there were no serious AEs related to vaccination. 80% of baseline SARS-CoV-2 naïve individuals (147/183) seroconverted two weeks post second immunization, irrespective of age (18–75); 56% (102/183) had detectable neutralising antibodies. Almost all (28/31) SARS-CoV-2 positive individuals had increased S IgG binding antibodies following their first 1.0 μg dose with a ≥0.5log10 increase in 71% (22/31). Encapsulated saRNA was well tolerated and immunogenic in adults aged 18–75 years. Seroconversion rates in antigen naïve were higher than those reported in our dose-ranging study. Further work is required to determine if this difference is related to a longer dosing interval (14 vs. 4 weeks) or dosing with 1.0 μg followed by 10.0 μg. Boosting of S IgG antibodies was observed with a single 1.0 μg injection in those with pre-existing immune responses. Grants and gifts from the UKRI (MC_PC_19076), the /Vaccine Task Force, , , , , and .
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影响因子：
64.5
作者：
Payne RP;Longet S;Austin JA;Skelly DT;Dejnirattisai W;Adele S;Meardon N;Faustini S;Al-Taei S;Moore SC;Tipton T;Hering LM;Angyal A;Brown R;Nicols AR;Gillson N;Dobson SL;Amini A;Supasa P;Cross A;Bridges-Webb A;Reyes LS;Linder A;Sandhar G;Kilby JA;Tyerman JK;Altmann T;Hornsby H;Whitham R;Phillips E;Malone T;Hargreaves A;Shields A;Saei A;Foulkes S;Stafford L;Johnson S;Wootton DG;Conlon CP;Jeffery K;Matthews PC;Frater J;Deeks AS;Pollard AJ;Brown A;Rowland-Jones SL;Mongkolsapaya J;Barnes E;Hopkins S;Hall V;Dold C;Duncan CJA;Richter A;Carroll M;Screaton G;de Silva TI;Turtle L;Klenerman P;Dunachie S;PITCH Consortium
通讯作者：
PITCH Consortium
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
DOI：
10.1016/s0140-6736(21)00432-3
发表时间：
2021-03-06
期刊：
Lancet (London, England)
影响因子：
--
作者：
Voysey M;Costa Clemens SA;Madhi SA;Weckx LY;Folegatti PM;Aley PK;Angus B;Baillie VL;Barnabas SL;Bhorat QE;Bibi S;Briner C;Cicconi P;Clutterbuck EA;Collins AM;Cutland CL;Darton TC;Dheda K;Dold C;Duncan CJA;Emary KRW;Ewer KJ;Flaxman A;Fairlie L;Faust SN;Feng S;Ferreira DM;Finn A;Galiza E;Goodman AL;Green CM;Green CA;Greenland M;Hill C;Hill HC;Hirsch I;Izu A;Jenkin D;Joe CCD;Kerridge S;Koen A;Kwatra G;Lazarus R;Libri V;Lillie PJ;Marchevsky NG;Marshall RP;Mendes AVA;Milan EP;Minassian AM;McGregor A;Mujadidi YF;Nana A;Padayachee SD;Phillips DJ;Pittella A;Plested E;Pollock KM;Ramasamy MN;Ritchie AJ;Robinson H;Schwarzbold AV;Smith A;Song R;Snape MD;Sprinz E;Sutherland RK;Thomson EC;Török ME;Toshner M;Turner DPJ;Vekemans J;Villafana TL;White T;Williams CJ;Douglas AD;Hill AVS;Lambe T;Gilbert SC;Pollard AJ;Oxford COVID Vaccine Trial Group
通讯作者：
Oxford COVID Vaccine Trial Group
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
影响因子：
16.6
作者：
Amirthalingam G;Bernal JL;Andrews NJ;Whitaker H;Gower C;Stowe J;Tessier E;Subbarao S;Ireland G;Baawuah F;Linley E;Warrener L;O'Brien M;Whillock C;Moss P;Ladhani SN;Brown KE;Ramsay ME
通讯作者：
Ramsay ME