State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics; National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health & School of Life Sciences, Xiamen University, 361102, Xiamen, Fujian, China.
Tsinghua-Peking Center for Life Sciences, Laboratory of Dynamic Immunobiology, School of Medicine, Tsinghua University, 100084, Beijing, China.
Nat Commun. 2023 Jul 11;14(1):4117. doi: 10.1038/s41467-023-39560-9.
The emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants and "anatomical escape" characteristics threaten the effectiveness of current coronavirus disease 2019 (COVID-19) vaccines. There is an urgent need to understand the immunological mechanism of broad-spectrum respiratory tract protection to guide broader vaccines development. Here we investigate immune responses induced by an NS1-deleted influenza virus vectored intranasal COVID-19 vaccine (dNS1-RBD) which provides broad-spectrum protection against SARS-CoV-2 variants in hamsters. Intranasal delivery of dNS1-RBD induces innate immunity, trained immunity and tissue-resident memory T cells covering the upper and lower respiratory tract. It restrains the inflammatory response by suppressing early phase viral load post SARS-CoV-2 challenge and attenuating pro-inflammatory cytokine (Il6, Il1b, and Ifng) levels, thereby reducing excess immune-induced tissue injury compared with the control group. By inducing local cellular immunity and trained immunity, intranasal delivery of NS1-deleted influenza virus vectored vaccine represents a broad-spectrum COVID-19 vaccine strategy to reduce disease burden.
严重急性呼吸综合征冠状病毒 2(SARS-CoV-2)变体的出现和“解剖逃逸”特征威胁着当前 2019 年冠状病毒病(COVID-19)疫苗的有效性。迫切需要了解广谱呼吸道保护的免疫机制,以指导更广泛的疫苗开发。在这里,我们研究了由缺失 NS1 的流感病毒载体鼻内 COVID-19 疫苗(dNS1-RBD)引起的免疫反应,该疫苗在仓鼠中提供针对 SARS-CoV-2 变体的广谱保护。鼻内递送 dNS1-RBD 可诱导先天免疫、训练免疫和组织驻留记忆 T 细胞,覆盖上呼吸道和下呼吸道。它通过抑制 SARS-CoV-2 挑战后早期病毒载量并降低促炎细胞因子(Il6、Il1b 和 Ifng)水平来抑制炎症反应,从而与对照组相比减少过度免疫诱导的组织损伤。通过诱导局部细胞免疫和训练免疫,缺失 NS1 的流感病毒载体疫苗的鼻内递送代表了一种减少疾病负担的广谱 COVID-19 疫苗策略。