Jearanaiwitayakul Tuksin, Limthongkul Jitra, Kaofai Chernkhwan, Apichirapokey Suttikarn, Chawengkirttikul Runglawan, Sapsutthipas Sompong, Sunintaboon Panya, Ubol Sukathida
Department of Microbiology, Faculty of Science, Mahidol University, Bangkok 10400, Thailand.
Institute of Biological Products, Department of Medical Sciences, Ministry of Public Health, Nonthaburi 11000, Thailand.
Biomedicines. 2022 May 16;10(5):1142. doi: 10.3390/biomedicines10051142.
The respiratory organ serves as a primary target site for SARS-CoV-2. Thus, the vaccine-stimulating immune response of the respiratory tract is significant in controlling SARS-CoV-2 transmission and disease development. In this study, mucoadhesive nanoparticles were used to deliver SARS-CoV-2 spike proteins (S-NPs) into the nasal tracts of mice. The responses in the respiratory organ and the systemic responses were monitored. The administration of S-NPs along with cGAMP conferred a robust stimulation of antibody responses in the respiratory tract, as demonstrated by an increase of IgA and IgG antibodies toward the spike proteins in bronchoalveolar lavages (BALs) and the lungs. Interestingly, the elicited antibodies were able to neutralize both the wild-type and Delta variant strains of SARS-CoV-2. Significantly, the intranasal immunization also stimulated systemic responses. This is evidenced by the increased production of circulating IgG and IgA, which were able to neutralize and bind specifically to the SARS-CoV-2 virion and spike protein. Additionally, this intranasal administration potently activated a splenic T cell response and the production of Th-1 cytokines, suggesting that this vaccine may well activate a cellular response in the respiratory tract. The results demonstrate that STING agonist strongly acts as an adjuvant to the immunogenicity of S-NPs. This platform may be an ideal vaccine against SARS-CoV-2.
呼吸器官是严重急性呼吸综合征冠状病毒2（SARS-CoV-2）的主要靶位点。因此，刺激呼吸道免疫反应的疫苗对于控制SARS-CoV-2传播和疾病发展具有重要意义。在本研究中，使用黏膜黏附纳米颗粒将SARS-CoV-2刺突蛋白（S-NPs）递送至小鼠鼻腔。监测呼吸器官的反应和全身反应。如支气管肺泡灌洗（BAL）液和肺中针对刺突蛋白的IgA和IgG抗体增加所示，S-NPs与环鸟苷酸-腺苷酸（cGAMP）联合给药可在呼吸道中强烈刺激抗体反应。有趣的是，所引发的抗体能够中和SARS-CoV-2的野生型和Delta变异株。值得注意的是，鼻内免疫也刺激了全身反应。循环IgG和IgA产量增加证明了这一点，它们能够中和并特异性结合SARS-CoV-2病毒粒子和刺突蛋白。此外，这种鼻内给药有力地激活了脾脏T细胞反应和Th-1细胞因子的产生，表明这种疫苗很可能在呼吸道中激活细胞反应。结果表明，干扰素基因刺激蛋白（STING）激动剂强烈增强S-NPs的免疫原性。该平台可能是一种理想的抗SARS-CoV-2疫苗。
