Recombinant Mycobacterium paragordonae Expressing SARS-CoV-2 Receptor-Binding Domain as a Vaccine Candidate Against SARS-CoV-2 Infections.
Recombinant Mycobacterium paragordonae Expressing SARS-CoV-2 Receptor-Binding Domain as a Vaccine Candidate Against SARS-CoV-2 Infections.
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DOI：
10.3389/fimmu.2021.712274
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发表时间：
2021
影响因子：
7.3
通讯作者：
Kim BJ
中科院分区：
文献类型：
--
作者：
Kim BJ;Jeong H;Seo H;Lee MH;Shin HM;Kim BJ
目前，人们担心最近全球出现的SARS-CoV-2变异体可能会损害目前的疫苗，这突出了对能够引发T细胞介导的免疫应答以及B细胞介导的中和抗体产生的新疫苗的迫切需求。在这项研究中，我们开发了一种新的表达SARS-CoV-2受体结合结构域（RBD）的重组副戈登分枝杆菌（rMpg-RBD-7），能够在接种疫苗的小鼠中引发RBD特异性免疫应答。rMpg-RBD-7作为SARS-CoV-2感染疫苗的潜在用途在体内使用两种不同模块的小鼠模型进行了评估，一种用于单剂量疫苗接种，另一种用于两剂量疫苗接种。在单剂量疫苗接种模型中，我们发现rMpg-RBD-7与热灭活菌株相比可以发挥增强的细胞介导的免疫（CMI）应答，以及能够中和RBD和ACE 2相互作用的体液免疫应答。在两剂疫苗接种模型中，与单剂rMpg-RBD疫苗接种或两剂RBD蛋白免疫相比，两剂疫苗接种中的rMpg-RBD-7也可以产生更强的CMI和体液免疫应答，以中和假病毒或活病毒感染系统中的SARS-CoV-2感染。总之，我们的数据表明，rMpg-RBD-7可以导致增强的CMI反应和体液免疫反应的小鼠接种单剂量或两剂量疫苗，突出了其作为一种新的疫苗候选人的可行性SARS-CoV-2。据我们所知，这项研究是第一个使用分枝杆菌作为SARS-CoV-2疫苗的递送系统。
At present, concerns that the recent global emergence of SARS-CoV-2 variants could compromise the current vaccines have been raised, highlighting the urgent demand for new vaccines capable of eliciting T cell-mediated immune responses, as well as B cell-mediated neutralizing antibody production. In this study, we developed a novel recombinant Mycobacterium paragordonae expressing the SARS-CoV-2 receptor-binding domain (RBD) (rMpg-RBD-7) that is capable of eliciting RBD-specific immune responses in vaccinated mice. The potential use of rMpg-RBD-7 as a vaccine for SARS-CoV-2 infections was evaluated in in vivo using mouse models of two different modules, one for single-dose vaccination and the other for two-dose vaccination. In a single-dose vaccination model, we found that rMpg-RBD-7 versus a heat-killed strain could exert an enhanced cell-mediated immune (CMI) response, as well as a humoral immune response capable of neutralizing the RBD and ACE2 interaction. In a two-dose vaccination model, rMpg-RBD-7 in a two-dose vaccination could also exert a stronger CMI and humoral immune response to neutralize SARS-CoV-2 infections in pseudoviral or live virus infection systems, compared to single dose vaccinations of rMpg-RBD or two-dose RBD protein immunization. In conclusion, our data showed that rMpg-RBD-7 can lead to an enhanced CMI response and humoral immune responses in mice vaccinated with both single- or two-dose vaccination, highlighting its feasibility as a novel vaccine candidate for SARS-CoV-2. To the best of our knowledge, this study is the first in which mycobacteria is used as a delivery system for a SARS-CoV-2 vaccine.
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影响因子：
13.2
作者：
Chan, Jasper Fuk-Woo;Kok, Kin-Hang;Yuen, Kwok-Yung
通讯作者：
Yuen, Kwok-Yung
影响因子：
168.9
作者：
Huang, Chaolin;Wang, Yeming;Cao, Bin
通讯作者：
Cao, Bin
影响因子：
3.1
作者：
Ferraz, JC;Stavropoulos, E;Tascon, RE
通讯作者：
Tascon, RE
影响因子：
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作者：
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通讯作者：
Kim BJ
影响因子：
3.7
作者：
Chapman R;Jongwe TI;Douglass N;Chege G;Williamson AL
通讯作者：
Williamson AL