Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

The Chimeric Adenovirus(Ad5/35) Expressing Engineered Spike Protein Confers Immunity Against SARS-Cov-2 in Mice and Non-Human Primates

Version 1 : Received: 7 April 2022 / Approved: 8 April 2022 / Online: 8 April 2022 (05:03:04 CEST)

A peer-reviewed article of this Preprint also exists.

Shin, S.-P.; Shin, K.-S.; Lee, J.-M.; Jung, I.-K.; Koo, J.; Lee, S.-W.; Park, S.; Shin, J.; Park, M.; Park, B.; Oh, H.; Koo, B.-S.; Hong, J.; Ryu, C.-M.; Kim, J.-O.; Oh, T.; Kang, C.-Y. The Chimeric Adenovirus (Ad5/35) Expressing Engineered Spike Protein Confers Immunity against SARS-CoV-2 in Mice and Non-Human Primates. Vaccines 2022, 10, 712. Shin, S.-P.; Shin, K.-S.; Lee, J.-M.; Jung, I.-K.; Koo, J.; Lee, S.-W.; Park, S.; Shin, J.; Park, M.; Park, B.; Oh, H.; Koo, B.-S.; Hong, J.; Ryu, C.-M.; Kim, J.-O.; Oh, T.; Kang, C.-Y. The Chimeric Adenovirus (Ad5/35) Expressing Engineered Spike Protein Confers Immunity against SARS-CoV-2 in Mice and Non-Human Primates. Vaccines 2022, 10, 712.

Abstract

Several COVID-19 platforms have been licensed across the world thus far, but vaccine platforms research that can lead to effective antigen delivery is still ongoing. Here, we constructed AdCLD-CoV19 that could modulate humoral immunity by harboring SARS-CoV-2 antigens onto a chimeric adenovirus 5/35 platform that was effective in cellular immunity. By replacing the S1/S2 furin cleavage sequence of the SARS-CoV-2 Spike (S) protein mounted on AdCLD-CoV19 with the linker sequence, high antigen expression was confirmed in various cell lines. The high levels of antigen expression contributed to antigen-specific antibody activity in mice and non-human primates (NHPs) with single vaccination of AdCLD-CoV19. Furthermore, the adenovirus-induced Th1 immune response was specifically raised for the S protein, and these immune responses protected the NHP against live viruses. While AdCLD-CoV19 maintained neutralizing antibody activity against various SARS-CoV-2 variants, it was reduced to single vaccination for β and ο variants, and the reduced neutralizing antibody activity was restored with booster shots. Hence, AdCLD-CoV19 can prevent SARS-CoV-2 with single vaccination, and the new vaccine administration strategy that responds to various variants can maintain the efficacy of the vaccine.

Keywords

SARS-CoV-2; Variants; COVID-19 vaccine; Chimeric adenovirus-vectored vaccine; GS linker; Neutralizing activity; Th1 immune responses

Subject

Biology and Life Sciences, Immunology and Microbiology

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