Single-Dose Intranasal Immunisation with Novel Chimeric H1N1 Expressing the Receptor-Binding Domain of SARS-CoV-2 Induces Robust Mucosal Immunity, Tissue-Resident Memory T Cells, and Heterologous Protection in Mice

Donghong Wang; Yao Deng; Jianfang Zhou; Wen Wang; Baoying Huang; Wenling Wang; Lan Wei; Jiao Ren; Ruiwen Han; Jialuo Bing; Chengcheng Zhai; Xiaoyan Guo; Wenjie Tan

doi:10.3390/vaccines11091453

Single-Dose Intranasal Immunisation with Novel Chimeric H1N1 Expressing the Receptor-Binding Domain of SARS-CoV-2 Induces Robust Mucosal Immunity, Tissue-Resident Memory T Cells, and Heterologous Protection in Mice

Vaccines (Basel). 2023 Sep 4;11(9):1453. doi: 10.3390/vaccines11091453.

Authors

Donghong Wang¹, Yao Deng¹, Jianfang Zhou², Wen Wang¹, Baoying Huang¹, Wenling Wang¹, Lan Wei¹, Jiao Ren¹, Ruiwen Han^{1

3}, Jialuo Bing^{1

4}, Chengcheng Zhai¹, Xiaoyan Guo¹, Wenjie Tan^{1

3

4}

Affiliations

¹ Key Laboratory of Biosafety, National Health Commissions, National Institute for Viral Disease Control and Prevention, China CDC, 155 Changbai Road, Beijing 102206, China.
² State Key Laboratory for Molecular Virology and Genetic Engineering, Chinese National Influenza Center, National Institute for Viral Disease Control and Prevention, China CDC, 155 Changbai Road, Beijing 102206, China.
³ Zhejiang Provincial Key Laboratory of Medical Genetics, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou 325035, China.
⁴ School of Public Health, Xinxiang Medical University, Xinxiang 453003, China.

Abstract

Current COVID-19 vaccines can effectively reduce disease severity and hospitalisation; however, they are not considerably effective in preventing infection and transmission. In this context, mucosal vaccines are pertinent to prevent SARS-CoV-2 infection and spread. In this study, we generated a replication-competent recombinant chimeric influenza A virus (IAV) expressing the receptor-binding domain (RBD) of a SARS-CoV-2 prototype in the C-terminus of the neuraminidase (NA) of A/Puerto Rico/08/1934 H1N1 (PR8). The remaining seven segments from A/WSN/1933 H1N1 (WSN) were named PR8NARBD/WSN. We observed that the recombinant virus with the WSN backbone demonstrated improved expression of NA and RBD. A single intranasal dose of PR8NARBD/WSN(10³PFU) in mice generated robust mucosal immunity, neutralising antibodies, cellular immunity, and tissue-resident memory T cells specific to SARS-CoV-2 and IAV. Importantly, immunisation with PR8NARBD/WSN viruses effectively protected mice against lethal challenges with H1N1, H3N2 IAV, and SARS-CoV-2 Beta variant and significantly reduced lung viral loads. Overall, our research demonstrates the promising potential of PR8NARBD/WSN as an attractive vaccine against emerging SARS-CoV-2 variants and influenza A virus infections.

Keywords: COVID-19; T cell immunity; heterologous protection; influenza virus; recombinant vaccine.

Abstract

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