The Chimeric Adenovirus (Ad5/35) Expressing Engineered Spike Protein Confers Immunity against SARS-CoV-2 in Mice and Non-Human Primates
Several COVID-19 platforms have been licensed across the world thus far, but vaccine platform 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...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-04-01
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| Series: | Vaccines |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2076-393X/10/5/712 |
| _version_ | 1797494870170927104 |
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| author | Seung-Phil Shin Kwang-Soo Shin Jeong-Mi Lee In-Kyung Jung Jimo Koo Seung-Woo Lee Seowoo Park Jieun Shin Myunghwan Park Bongju Park Hanseul Oh Bon-Sang Koo Jungjoo Hong Choong-Min Ryu Jae-Ouk Kim Taegwon Oh Chang-Yuil Kang |
| author_facet | Seung-Phil Shin Kwang-Soo Shin Jeong-Mi Lee In-Kyung Jung Jimo Koo Seung-Woo Lee Seowoo Park Jieun Shin Myunghwan Park Bongju Park Hanseul Oh Bon-Sang Koo Jungjoo Hong Choong-Min Ryu Jae-Ouk Kim Taegwon Oh Chang-Yuil Kang |
| author_sort | Seung-Phil Shin |
| collection | DOAJ |
| description | Several COVID-19 platforms have been licensed across the world thus far, but vaccine platform 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 a single vaccination of AdCLD-CoV19. Furthermore, the adenovirus-induced T<sub>h</sub>1 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 a single vaccination, and the new vaccine administration strategy that responds to various variants can maintain the efficacy of the vaccine. |
| first_indexed | 2024-03-10T01:40:31Z |
| format | Article |
| id | doaj.art-8e67b259b29c4f68ae9f11342ff14fd7 |
| institution | Directory Open Access Journal |
| issn | 2076-393X |
| language | English |
| last_indexed | 2024-03-10T01:40:31Z |
| publishDate | 2022-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Vaccines |
| spelling | doaj.art-8e67b259b29c4f68ae9f11342ff14fd72023-11-23T13:25:59ZengMDPI AGVaccines2076-393X2022-04-0110571210.3390/vaccines10050712The Chimeric Adenovirus (Ad5/35) Expressing Engineered Spike Protein Confers Immunity against SARS-CoV-2 in Mice and Non-Human PrimatesSeung-Phil Shin0Kwang-Soo Shin1Jeong-Mi Lee2In-Kyung Jung3Jimo Koo4Seung-Woo Lee5Seowoo Park6Jieun Shin7Myunghwan Park8Bongju Park9Hanseul Oh10Bon-Sang Koo11Jungjoo Hong12Choong-Min Ryu13Jae-Ouk Kim14Taegwon Oh15Chang-Yuil Kang16Cellid Co., Ltd., Seoul 08826, KoreaCellid Co., Ltd., Seoul 08826, KoreaCellid Co., Ltd., Seoul 08826, KoreaCellid Co., Ltd., Seoul 08826, KoreaCellid Co., Ltd., Seoul 08826, KoreaCellid Co., Ltd., Seoul 08826, KoreaCellid Co., Ltd., Seoul 08826, KoreaCellid Co., Ltd., Seoul 08826, KoreaCellid Co., Ltd., Seoul 08826, KoreaCellid Co., Ltd., Seoul 08826, KoreaNational Primate Research Center, Korea Research Institute of Bioscience and Biotechnology, Cheongju 28116, KoreaNational Primate Research Center, Korea Research Institute of Bioscience and Biotechnology, Cheongju 28116, KoreaNational Primate Research Center, Korea Research Institute of Bioscience and Biotechnology, Cheongju 28116, KoreaInfectious Disease Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 34141, KoreaScience Unit, International Vaccine Institute, Seoul 08826, KoreaCellid Co., Ltd., Seoul 08826, KoreaCellid Co., Ltd., Seoul 08826, KoreaSeveral COVID-19 platforms have been licensed across the world thus far, but vaccine platform 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 a single vaccination of AdCLD-CoV19. Furthermore, the adenovirus-induced T<sub>h</sub>1 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 a single vaccination, and the new vaccine administration strategy that responds to various variants can maintain the efficacy of the vaccine.https://www.mdpi.com/2076-393X/10/5/712SARS-CoV-2variantsCOVID-19 vaccinechimeric adenovirus-vectored vaccineGS linkerneutralizing activity |
| spellingShingle | Seung-Phil Shin Kwang-Soo Shin Jeong-Mi Lee In-Kyung Jung Jimo Koo Seung-Woo Lee Seowoo Park Jieun Shin Myunghwan Park Bongju Park Hanseul Oh Bon-Sang Koo Jungjoo Hong Choong-Min Ryu Jae-Ouk Kim Taegwon Oh Chang-Yuil Kang The Chimeric Adenovirus (Ad5/35) Expressing Engineered Spike Protein Confers Immunity against SARS-CoV-2 in Mice and Non-Human Primates Vaccines SARS-CoV-2 variants COVID-19 vaccine chimeric adenovirus-vectored vaccine GS linker neutralizing activity |
| title | The Chimeric Adenovirus (Ad5/35) Expressing Engineered Spike Protein Confers Immunity against SARS-CoV-2 in Mice and Non-Human Primates |
| title_full | The Chimeric Adenovirus (Ad5/35) Expressing Engineered Spike Protein Confers Immunity against SARS-CoV-2 in Mice and Non-Human Primates |
| title_fullStr | The Chimeric Adenovirus (Ad5/35) Expressing Engineered Spike Protein Confers Immunity against SARS-CoV-2 in Mice and Non-Human Primates |
| title_full_unstemmed | The Chimeric Adenovirus (Ad5/35) Expressing Engineered Spike Protein Confers Immunity against SARS-CoV-2 in Mice and Non-Human Primates |
| title_short | The Chimeric Adenovirus (Ad5/35) Expressing Engineered Spike Protein Confers Immunity against SARS-CoV-2 in Mice and Non-Human Primates |
| title_sort | chimeric adenovirus ad5 35 expressing engineered spike protein confers immunity against sars cov 2 in mice and non human primates |
| topic | SARS-CoV-2 variants COVID-19 vaccine chimeric adenovirus-vectored vaccine GS linker neutralizing activity |
| url | https://www.mdpi.com/2076-393X/10/5/712 |
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