Immunogenic potential of DNA vaccine candidate, ZyCoV-D against SARS-CoV-2 in animal models.

Immunogenic potential of DNA vaccine candidate, ZyCoV-D against SARS-CoV-2 in animal models.
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DOI:
10.1016/j.vaccine.2021.05.098
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发表时间:
2021-07-05
期刊:
影响因子:
5.5
通讯作者:
Maithal K
Maithal K
中科院分区:
医学3区
文献类型:
--
作者:
Dey A;Chozhavel Rajanathan TM;Chandra H;Pericherla HPR;Kumar S;Choonia HS;Bajpai M;Singh AK;Sinha A;Saini G;Dalal P;Vandriwala S;Raheem MA;Divate RD;Navlani NL;Sharma V;Parikh A;Prasath S;Sankar Rao M;Maithal K

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严重急性呼吸道综合征冠状病毒2型(SARS-CoV-2)于2019年首次起源于中国,并在5个月内迅速蔓延至地球仪,造成超过9600万例感染和超过200万例死亡。我们作出了巨大努力,使COVID-19疫苗进入临床开发,以便如果在试验中发现有效,可以尽早提供。我们开发了一种候选疫苗ZyCoV-D,该疫苗由携带编码SARS-CoV-2病毒刺突蛋白(S)的基因的DNA质粒载体组成。该病毒的S蛋白包括受体结合结构域(RBD),负责与人血管紧张素转换酶(ACE-2)受体结合。将该质粒转化E.大肠杆菌细胞进行大规模生产。在小鼠、豚鼠和兔模型中,通过皮内途径以25、100和500 µg剂量评价了质粒DNA的免疫原性潜力。基于动物研究,已建立概念验证,并在大鼠和家兔模型中进行了临床前毒理学(PCT)研究。初步的动物实验表明,候选DNA疫苗诱导抗体应答,包括针对SARS-CoV-2的中和抗体,还诱导Th-1应答,如通过升高的IFN-γ水平所证明的。
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), initially originated in China in year 2019 and spread rapidly across the globe within 5 months, causing over 96 million cases of infection and over 2 million deaths. Huge efforts were undertaken to bring the COVID-19 vaccines in clinical development, so that it can be made available at the earliest, if found to be efficacious in the trials. We developed a candidate vaccine ZyCoV-D comprising of a DNA plasmid vector carrying the gene encoding the spike protein (S) of the SARS-CoV-2 virus. The S protein of the virus includes the receptor binding domain (RBD), responsible for binding to the human angiotensin converting enzyme (ACE-2) receptor. The DNA plasmid construct was transformed into E. coli cells for large scale production. The immunogenicity potential of the plasmid DNA has been evaluated in mice, guinea pig, and rabbit models by intradermal route at 25, 100 and 500 µg dose. Based on the animal studies proof-of-concept has been established and preclinical toxicology (PCT) studies were conducted in rat and rabbit model. Preliminary animal study demonstrates that the candidate DNA vaccine induces antibody response including neutralizing antibodies against SARS-CoV-2 and also elicited Th-1 response as evidenced by elevated IFN-γ levels.
BNT162B2 mRNA COVID-19疫苗的安全性和功效。
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