Division of Enzyme Chemistry, Institute for Enzyme Research Tokushima University Tokushima Japan.
Faculty of Pharmaceutical Sciences Tokushima University Tokushima Japan.
Influenza Other Respir Viruses. 2023 Mar 9;17(3):e13119. doi: 10.1111/irv.13119. eCollection 2023 Mar.
There is a need for vaccines that can induce effective systemic, respiratory mucosal, and cellular immunity to control the COVID-19 pandemic. We reported previously that a synthetic mucosal adjuvant SF-10 derived from human pulmonary surfactant works as an efficient antigen delivery vehicle to antigen presenting cells in the respiratory and gastrointestinal tracts and promotes induction of influenza virus antigen-specific serum IgG, mucosal IgA, and cellular immunity.
The aim of the present study was to determine the effectiveness of a new administration route of trans-airway (TA) vaccine comprising recombinant SARS-CoV-2 spike protein 1 (S1) combined with SF-10 (S1-SF-10 vaccine) on systemic, local, and cellular immunity in mice, compared with intramuscular injection (IM) of S1 with a potent adjuvant AddaS03™ (S1-AddaS03™ vaccine).
S1-SF-10-TA vaccine induced S1-specific IgG and IgA in serum and lung mucosae. These IgG and IgA induced by S1-SF-10-TA showed significant protective immunity in a receptor binding inhibition test of S1 and angiotensin converting enzyme 2, a receptor of SARS-CoV-2, which were more potent and faster achievement than S1-AddaS03™-IM. Enzyme-linked immunospot assay showed high numbers of S1-specific IgA and IgG secreting cells (ASCs) and S1-responsive IFN-γ, IL-4, IL-17A cytokine secreting cells (CSCs) in the spleen and lungs. S1-AddaS03™-IM induced IgG ASCs and IL-4 CSCs in spleen higher than S1-SF-10-TA, but the numbers of ASCs and CSCs in lungs were low and hardly detected.
Based on the need for effective systemic, respiratory, and cellular immunity, the S1-SF-10-TA vaccine seems promising mucosal vaccine against respiratory infection of SARS-CoV-2.
需要能够诱导有效全身、呼吸道黏膜和细胞免疫的疫苗来控制 COVID-19 大流行。我们之前报道过，一种源自人肺表面活性剂的合成黏膜佐剂 SF-10 可作为一种有效的抗原递呈细胞载体，递呈给呼吸道和胃肠道中的抗原提呈细胞，并促进流感病毒抗原特异性血清 IgG、黏膜 IgA 和细胞免疫的产生。
本研究旨在确定经气道（TA）途径给药的新型疫苗的有效性，该疫苗由重组 SARS-CoV-2 刺突蛋白 1（S1）与 SF-10 组成（S1-SF-10 疫苗），与肌肉内注射（IM）含有效佐剂 AddaS03™的 S1（S1-AddaS03™疫苗）相比，在小鼠中的系统、局部和细胞免疫方面的效果。
S1-SF-10-TA 疫苗诱导 S1 特异性 IgG 和 IgA 在血清和肺黏膜中产生。与 SARS-CoV-2 受体血管紧张素转换酶 2（ACE2）的 S1 受体结合抑制试验相比，S1-SF-10-TA 诱导的这些 IgG 和 IgA 显示出显著的保护免疫作用，其效果更强大且更快实现，优于 S1-AddaS03™-IM。酶联免疫斑点试验显示 S1 特异性 IgA 和 IgG 分泌细胞（ASC）和 S1 反应性 IFN-γ、IL-4、IL-17A 细胞因子分泌细胞（CSC）在脾和肺中数量较高。与 S1-SF-10-TA 相比，S1-AddaS03™-IM 诱导脾中 IgG ASC 和 IL-4 CSC 的数量更高，但肺中的 ASC 和 CSC 数量较低，难以检测到。
基于对有效全身、呼吸道和细胞免疫的需求，S1-SF-10-TA 疫苗似乎是一种有前途的针对 SARS-CoV-2 呼吸道感染的黏膜疫苗。
