Fc-binding nanodisc restores antiviral efficacy of antibodies with reduced neutralizing effects against evolving SARS-CoV-2 variants
Abstract Passive antibody therapies, typically administered via parenteral routes, have played a crucial role in the initial response to the COVID-19 pandemic. However, the ongoing evolution of SARS-CoV-2 has revealed significant limitations of this approach, primarily due to mutational escape and t...
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| Format: | Article |
| Language: | English |
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BMC
2025-01-01
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| Series: | Journal of Nanobiotechnology |
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| Online Access: | https://doi.org/10.1186/s12951-025-03100-y |
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| author | Jaehyeon Hwang Soyun Choi Beom Kyu Kim Sumin Son Jeong Hyeon Yoon Kyung Won Kim Wonbeom Park Hyunjoo Choo Suhyun Kim Soomin Kim Seokhyeon Yu Sangwon Jung Sang Taek Jung Min-Suk Song Sang Jick Kim Dae-Hyuk Kweon |
| author_facet | Jaehyeon Hwang Soyun Choi Beom Kyu Kim Sumin Son Jeong Hyeon Yoon Kyung Won Kim Wonbeom Park Hyunjoo Choo Suhyun Kim Soomin Kim Seokhyeon Yu Sangwon Jung Sang Taek Jung Min-Suk Song Sang Jick Kim Dae-Hyuk Kweon |
| author_sort | Jaehyeon Hwang |
| collection | DOAJ |
| description | Abstract Passive antibody therapies, typically administered via parenteral routes, have played a crucial role in the initial response to the COVID-19 pandemic. However, the ongoing evolution of SARS-CoV-2 has revealed significant limitations of this approach, primarily due to mutational escape and the inadequate delivery of antibodies to the upper respiratory tract. To overcome these challenges, we propose a novel prophylactic strategy involving the intranasal delivery of an antibody in combination with an Fc-binding nanodisc. This nanodisc, engineered to specifically bind to the Fc regions of IgG antibodies, served two key functions: extending the antibody's half-life in the larynx and trachea, and enhancing its neutralization efficacy. Notably, Sotrovimab, an FDA-approved monoclonal antibody that has experienced a significant decline in neutralizing potency due to viral evolution, exhibited robust antiviral activity when complexed with the nanodisc against all tested Omicron variants. Furthermore, the Fc-binding nanodisc significantly boosted the antiviral efficacy of the soluble angiotensin-converting enzyme 2 (sACE2) Fc fusion protein, which possesses broad but modest antiviral activity. In ACE2 transgenic mice, the Fc-binding nanodisc protected better than sACE2-Fc alone with two more log reduction in lung viral titer. Therefore, the intranasal Fc-binding nanodisc offers a promising and powerful approach to counteract the diminished antiviral activity of neutralizing antibodies caused by mutational escape, effectively restoring antiviral efficacy against various evolving SARS-CoV-2 variants. |
| format | Article |
| id | doaj-art-ebfd6f2c98ff4281b04e612f17a2f619 |
| institution | Kabale University |
| issn | 1477-3155 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Nanobiotechnology |
| spelling | doaj-art-ebfd6f2c98ff4281b04e612f17a2f6192025-01-26T12:50:54ZengBMCJournal of Nanobiotechnology1477-31552025-01-0123112010.1186/s12951-025-03100-yFc-binding nanodisc restores antiviral efficacy of antibodies with reduced neutralizing effects against evolving SARS-CoV-2 variantsJaehyeon Hwang0Soyun Choi1Beom Kyu Kim2Sumin Son3Jeong Hyeon Yoon4Kyung Won Kim5Wonbeom Park6Hyunjoo Choo7Suhyun Kim8Soomin Kim9Seokhyeon Yu10Sangwon Jung11Sang Taek Jung12Min-Suk Song13Sang Jick Kim14Dae-Hyuk Kweon15Department of Integrative Biotechnology, College of Biotechnology and Bioengineering, Sungkyunkwan UniversityDepartment of Integrative Biotechnology, College of Biotechnology and Bioengineering, Sungkyunkwan UniversityCollege of Medicine and Medical Research Institute, Chungbuk National UniversitySynthetic Biology Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)Department of Integrative Biotechnology, College of Biotechnology and Bioengineering, Sungkyunkwan UniversityDepartment of Integrative Biotechnology, College of Biotechnology and Bioengineering, Sungkyunkwan UniversityDepartment of Integrative Biotechnology, College of Biotechnology and Bioengineering, Sungkyunkwan UniversityDepartment of Integrative Biotechnology, College of Biotechnology and Bioengineering, Sungkyunkwan UniversityDepartment of Integrative Biotechnology, College of Biotechnology and Bioengineering, Sungkyunkwan UniversityDepartment of Integrative Biotechnology, College of Biotechnology and Bioengineering, Sungkyunkwan UniversityResearch Center, Mvrix Inc.Research Center, Mvrix Inc.School of Chemical and Biological Engineering, Seoul National UniversityCollege of Medicine and Medical Research Institute, Chungbuk National UniversitySynthetic Biology Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)Department of Integrative Biotechnology, College of Biotechnology and Bioengineering, Sungkyunkwan UniversityAbstract Passive antibody therapies, typically administered via parenteral routes, have played a crucial role in the initial response to the COVID-19 pandemic. However, the ongoing evolution of SARS-CoV-2 has revealed significant limitations of this approach, primarily due to mutational escape and the inadequate delivery of antibodies to the upper respiratory tract. To overcome these challenges, we propose a novel prophylactic strategy involving the intranasal delivery of an antibody in combination with an Fc-binding nanodisc. This nanodisc, engineered to specifically bind to the Fc regions of IgG antibodies, served two key functions: extending the antibody's half-life in the larynx and trachea, and enhancing its neutralization efficacy. Notably, Sotrovimab, an FDA-approved monoclonal antibody that has experienced a significant decline in neutralizing potency due to viral evolution, exhibited robust antiviral activity when complexed with the nanodisc against all tested Omicron variants. Furthermore, the Fc-binding nanodisc significantly boosted the antiviral efficacy of the soluble angiotensin-converting enzyme 2 (sACE2) Fc fusion protein, which possesses broad but modest antiviral activity. In ACE2 transgenic mice, the Fc-binding nanodisc protected better than sACE2-Fc alone with two more log reduction in lung viral titer. Therefore, the intranasal Fc-binding nanodisc offers a promising and powerful approach to counteract the diminished antiviral activity of neutralizing antibodies caused by mutational escape, effectively restoring antiviral efficacy against various evolving SARS-CoV-2 variants.https://doi.org/10.1186/s12951-025-03100-yAntibodySARS-CoV-2NanodiscAntiviralCOVID19 |
| spellingShingle | Jaehyeon Hwang Soyun Choi Beom Kyu Kim Sumin Son Jeong Hyeon Yoon Kyung Won Kim Wonbeom Park Hyunjoo Choo Suhyun Kim Soomin Kim Seokhyeon Yu Sangwon Jung Sang Taek Jung Min-Suk Song Sang Jick Kim Dae-Hyuk Kweon Fc-binding nanodisc restores antiviral efficacy of antibodies with reduced neutralizing effects against evolving SARS-CoV-2 variants Journal of Nanobiotechnology Antibody SARS-CoV-2 Nanodisc Antiviral COVID19 |
| title | Fc-binding nanodisc restores antiviral efficacy of antibodies with reduced neutralizing effects against evolving SARS-CoV-2 variants |
| title_full | Fc-binding nanodisc restores antiviral efficacy of antibodies with reduced neutralizing effects against evolving SARS-CoV-2 variants |
| title_fullStr | Fc-binding nanodisc restores antiviral efficacy of antibodies with reduced neutralizing effects against evolving SARS-CoV-2 variants |
| title_full_unstemmed | Fc-binding nanodisc restores antiviral efficacy of antibodies with reduced neutralizing effects against evolving SARS-CoV-2 variants |
| title_short | Fc-binding nanodisc restores antiviral efficacy of antibodies with reduced neutralizing effects against evolving SARS-CoV-2 variants |
| title_sort | fc binding nanodisc restores antiviral efficacy of antibodies with reduced neutralizing effects against evolving sars cov 2 variants |
| topic | Antibody SARS-CoV-2 Nanodisc Antiviral COVID19 |
| url | https://doi.org/10.1186/s12951-025-03100-y |
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