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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
Wang, D.; Deng, Y.; Zhou, J.; Wang, W.; Huang, B.; Wang, W.; Wei, L.; Ren, J.; Han, R.; Bing, J.; Zhai, C.; Guo, X.; Tan, W. 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. Vaccines2023, 11, 1453.
Wang, D.; Deng, Y.; Zhou, J.; Wang, W.; Huang, B.; Wang, W.; Wei, L.; Ren, J.; Han, R.; Bing, J.; Zhai, C.; Guo, X.; Tan, W. 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 2023, 11, 1453.
Wang, D.; Deng, Y.; Zhou, J.; Wang, W.; Huang, B.; Wang, W.; Wei, L.; Ren, J.; Han, R.; Bing, J.; Zhai, C.; Guo, X.; Tan, W. 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. Vaccines2023, 11, 1453.
Wang, D.; Deng, Y.; Zhou, J.; Wang, W.; Huang, B.; Wang, W.; Wei, L.; Ren, J.; Han, R.; Bing, J.; Zhai, C.; Guo, X.; Tan, W. 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 2023, 11, 1453.
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 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 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; Influenza virus; Heterologous protection; Recombinant vaccine; T cell immunity
Subject
Biology and Life Sciences, Virology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
