Kim Byoung-Jun, Jeong Hyein, Seo Hyejun, Lee Mi-Hyun, Shin Hyun Mu, Kim Bum-Joon
Department of Microbiology and Immunology, College of Medicine, Seoul National University, Seoul, South Korea.
Department of Biomedical Sciences, College of Medicine, Seoul National University, Seoul, South Korea.
Front Immunol. 2021 Aug 27;12:712274. doi: 10.3389/fimmu.2021.712274. eCollection 2021.
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 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 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 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.
目前，有人担心最近在全球出现的严重急性呼吸综合征冠状病毒2（SARS-CoV-2）变体可能会影响当前的疫苗，这凸显了对能够引发T细胞介导的免疫反应以及B细胞介导的中和抗体产生的新疫苗的迫切需求。在本研究中，我们开发了一种表达SARS-CoV-2受体结合域（RBD）的新型重组体（rMpg-RBD-7），它能够在接种疫苗的小鼠中引发RBD特异性免疫反应。使用两种不同模式的小鼠模型评估了rMpg-RBD-7作为SARS-CoV-2感染疫苗的潜在用途，一种用于单剂量接种，另一种用于两剂量接种。在单剂量接种模型中，我们发现rMpg-RBD-7与热灭活菌株相比，可增强细胞介导的免疫（CMI）反应以及能够中和RBD与血管紧张素转换酶2（ACE2）相互作用的体液免疫反应。在两剂量接种模型中，与rMpg-RBD的单剂量接种或两剂量RBD蛋白免疫相比，两剂量接种的rMpg-RBD-7在假病毒或活病毒感染系统中对中和SARS-CoV-2感染也可产生更强的CMI和体液免疫反应。总之，我们的数据表明，rMpg-RBD-7在单剂量或两剂量接种的小鼠中均可导致增强的CMI反应和体液免疫反应，突出了其作为SARS-CoV-2新型候选疫苗的可行性。据我们所知，本研究是首次将分枝杆菌用作SARS-CoV-2疫苗的递送系统。
