Intranasal delivery of adenovirus-vectored vaccine confers protective mucosal immunity against SARS-CoV-2

Abstract The ongoing pandemic of COVID-19, caused by SARS-CoV-2 infection, has threatened the global health. Since the first case of infection was reported in December 2019, SARS-CoV-2 has rapidly spread all over the world and caused millions of deaths. As vaccination is the best way to protect the host from invading pathogens, several vaccines have been developed to prevent the infection of SARS-CoV-2 and saved huge numbers of lives so far. However, SARS-CoV-2 constantly change their antigens resulting in the escape from vaccine-induced protection, and the persistence of immunity induced by vaccine becomes an issue. Further, traditional intramuscular COVID-19 vaccines are insufficient to evoke mucosal specific immune response. Because the respiratory tract is the primary route of SARS-CoV-2 entry, the need for mucosal vaccine has been strongly suggested. Using adenoviral (Ad) vector platform, we generated recombinant COVID-19 vaccines that encode modified-spike antigen, and evaluated the vaccine efficacy in murine models. We found that intranasal delivery of Ad-vectored vaccines elicited both systemic as well as mucosal immune responses, and rescued mice from lethal SARS-CoV-2 infection. Further, we revealed that intranasal vaccination of Ad-vectored vaccines changed transcriptional landscape of lung. These results indicate that our recombinant Ad-vectored vaccine has the potential to confer protective immunity against SARS-CoV-2. This study was supported by the National Research Foundation of Korea (NRF-2021M3A9D3026428 and NRF-2021M3A9H3015688) funded by the Ministry of Science and ICT of Korea. This work was also supported by Mobile Clinic Module Project funded by KAIST and the 2020 Joint Research Project of Institutes of Science and Technology. H.E. Jung was supported by Basic Science Research Program through the NRF funded by the Ministry of Education (2022R1I1A1A01071399)