Renal Division, Department of Clinical Medicine, Faculty of Medicine, University of São Paulo, São Paulo, Brazil.
Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
PLoS One. 2022 May 24;17(5):e0268434. doi: 10.1371/journal.pone.0268434. eCollection 2022.
The SARS-CoV-2 pandemic have been affecting millions of people worldwide, since the beginning of 2020. COVID-19 can cause a wide range of clinical symptoms, which varies from asymptomatic presentation to severe respiratory insufficiency, exacerbation of immune response, disseminated microthrombosis and multiple organ failure, which may lead to dead. Due to the rapid spread of SARS-CoV-2, the development of vaccines to minimize COVID-19 severity in the world population is imperious. One of the employed techniques to produce vaccines against emerging viruses is the synthesis of recombinant proteins, which can be used as immunizing agents. Based on the exposed, the aim of the present study was to verify the systemic and immunological effects of IM administration of recombinant Nucleocapsid protein (NP), derived from SARS-CoV-2 and produced by this research group, in 2 different strains of rats (Rattus norvegicus); Wistar and Lewis. For this purpose, experimental animals received 4 injections of NP, once a week, and were submitted to biochemical and histological analysis. Our results showed that NP inoculations were safe for the animals, which presented no clinical symptoms of worrying side effects, nor laboratorial alterations in the main biochemical and histological parameters, suggesting the absence of toxicity induced by NP. Moreover, NP injections successfully triggered the production of specific anti-SARS-CoV-2 IgG antibodies by both Wistar and Lewis rats, showing the sensitization to have been well sufficient for the immunization of these strains of rats. Additionally, we observed the local lung activation of the Bronchus-Associated Lymphoid Tissue (BALT) of rats in the NP groups, suggesting that NP elicits specific lung immune response. Although pre-clinical and clinical studies are still required, our data support the recombinant NP produced by this research group as a potential immunizing agent for massive vaccination, and may represent advantages upon other recombinant proteins, since it seems to induce specific pulmonary protection.
自 2020 年初以来，SARS-CoV-2 大流行一直影响着全球数百万人。COVID-19 可引起广泛的临床症状，从无症状表现到严重呼吸功能不全、免疫反应加剧、弥散性微血栓形成和多器官衰竭不等，这可能导致死亡。由于 SARS-CoV-2 的迅速传播，开发疫苗以最大程度地减少世界人口中 COVID-19 的严重性迫在眉睫。用于生产针对新兴病毒疫苗的技术之一是合成重组蛋白，这些蛋白可用作免疫原。基于上述内容，本研究旨在验证 IM 给予源自 SARS-CoV-2 并由本研究小组生产的重组核衣壳蛋白（NP）对 2 种不同品系大鼠（Norvegicus 大鼠）的系统和免疫作用；Wistar 和 Lewis。为此，实验动物接受了 4 次 NP 接种，每周一次，并进行了生化和组织学分析。我们的结果表明，NP 接种对动物是安全的，它们没有出现令人担忧的副作用的临床症状，也没有主要生化和组织学参数的实验室改变，这表明 NP 没有引起毒性。此外，NP 注射成功地触发了 Wistar 和 Lewis 大鼠产生针对 SARS-CoV-2 的特异性 IgG 抗体，表明这两种大鼠的免疫致敏作用非常充分。此外，我们观察到 NP 组大鼠的肺部支气管相关淋巴组织（BALT）局部激活，表明 NP 引发了针对肺部的特异性免疫反应。尽管还需要进行临床前和临床研究，但我们的数据支持本研究小组生产的重组 NP 作为大规模疫苗接种的潜在免疫原，并且可能比其他重组蛋白具有优势，因为它似乎可以诱导针对肺部的特异性保护。
