Nature Communications (Jul 2023)

Intranasal influenza-vectored COVID-19 vaccine restrains the SARS-CoV-2 inflammatory response in hamsters

  • Liang Zhang,
  • Yao Jiang,
  • Jinhang He,
  • Junyu Chen,
  • Ruoyao Qi,
  • Lunzhi Yuan,
  • Tiange Shao,
  • Hui Zhao,
  • Congjie Chen,
  • Yaode Chen,
  • Xijing Wang,
  • Xing Lei,
  • Qingxiang Gao,
  • Chunlan Zhuang,
  • Ming Zhou,
  • Jian Ma,
  • Wei Liu,
  • Man Yang,
  • Rao Fu,
  • Yangtao Wu,
  • Feng Chen,
  • Hualong Xiong,
  • Meifeng Nie,
  • Yiyi Chen,
  • Kun Wu,
  • Mujin Fang,
  • Yingbin Wang,
  • Zizheng Zheng,
  • Shoujie Huang,
  • Shengxiang Ge,
  • Shih Chin Cheng,
  • Huachen Zhu,
  • Tong Cheng,
  • Quan Yuan,
  • Ting Wu,
  • Jun Zhang,
  • Yixin Chen,
  • Tianying Zhang,
  • Changgui Li,
  • Hai Qi,
  • Yi Guan,
  • Ningshao Xia

DOI
https://doi.org/10.1038/s41467-023-39560-9
Journal volume & issue
Vol. 14, no. 1
pp. 1 – 18

Abstract

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Abstract 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.