Preclinical evaluation of a candidate naked plasmid DNA vaccine against SARS-CoV-2.
Preclinical evaluation of a candidate naked plasmid DNA vaccine against SARS-CoV-2.
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DOI：
10.1038/s41541-021-00419-z
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发表时间：
2021-12-20
期刊：
影响因子：
9.2
通讯作者：
Fomsgaard A
中科院分区：
文献类型：
--
作者：
Lassaunière R;Polacek C;Gram GJ;Frische A;Tingstedt JL;Krüger M;Dorner BG;Cook A;Brown R;Orekov T;Putmon-Taylor T;Campbell TA;Greenhouse J;Pessaint L;Andersen H;Lewis MG;Fomsgaard A
新一代质粒DNA疫苗可能是一种安全、快速、简便的应急疫苗平台，用于预防新出现的病毒性病原体。应用平台优化策略，我们测试了一种针对严重急性呼吸综合征冠状病毒2型（SARS-CoV-2）的候选DNA质粒疫苗的临床前免疫原性和保护效果。该DNA疫苗在小鼠、兔和恒河猴中诱导尖峰特异性结合IgG和中和抗体，以及在小动物中诱导稳健的Th 1优势细胞应答。皮内和肌内无针注射DNA疫苗产生了相当的免疫应答。在一项对恒河猴进行的疫苗接种-攻毒研究中，证明了在鼻内和肺内接种SARS-CoV-2后，疫苗可防止病毒在肺中复制。总之，编码SARS-CoV-2刺突蛋白的候选质粒DNA疫苗在不同模型中具有免疫原性，并在非人灵长类动物中赋予针对肺部感染的保护。需要在临床试验中进一步评估这种DNA疫苗候选物。
New generation plasmid DNA vaccines may be a safe, fast and simple emergency vaccine platform for preparedness against emerging viral pathogens. Applying platform optimization strategies, we tested the pre-clinical immunogenicity and protective effect of a candidate DNA plasmid vaccine specific for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The DNA vaccine induced spike-specific binding IgG and neutralizing antibodies in mice, rabbits, and rhesus macaques together with robust Th1 dominant cellular responses in small animals. Intradermal and intramuscular needle-free administration of the DNA vaccine yielded comparable immune responses. In a vaccination-challenge study of rhesus macaques, the vaccine demonstrated protection from viral replication in the lungs following intranasal and intratracheal inoculation with SARS-CoV-2. In conclusion, the candidate plasmid DNA vaccine encoding the SARS-CoV-2 spike protein is immunogenic in different models and confers protection against lung infection in nonhuman primates. Further evaluation of this DNA vaccine candidate in clinical trials is warranted.
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