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J. Nanobiotechnol., Jan 24 2025, 23 (1) | https://doi.org/10.1186/s12951-025-03100-y Fc-binding nanodisc restores antiviral efficacy of antibodies with reduced neutralizing effects against evolving SARS-CoV-2 variants

Jaehyeon Hwang^1†, Soyun Choi^1†, Beom Kyu Kim², Sumin Son³, Jeong Hyeon Yoon¹, Kyung Won Kim¹, Wonbeom Park¹, Hyunjoo Choo¹, Suhyun Kim¹, Soomin Kim¹, Seokhyeon Yu⁴, Sangwon Jung⁴, Sang Taek Jung⁵, Min‑Suk Song^2*, Sang Jick Kim^3,6* and Dae‑Hyuk Kweon^1*

¹Department of Integrative Biotechnology, College of Biotechnology and Bioengineering, Sungkyunkwan University, Suwon 16419, Republic of Korea
²College of Medicine and Medical Research Institute, Chungbuk National University, Cheongju 28644, Republic of Korea
³Synthetic Biology Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, Republic of Korea
⁴Research Center, Mvrix Inc., Anyang 14058, Republic of Korea
⁵School of Chemical and Biological Engineering, Seoul National University, Seoul 08826, Republic of Korea
⁶Department of Biosystems and Bioengineering, KRIBB School of Biotechnology, University of Science & Technology (UST), Daejeon 34113, Republic of Korea
^†Jaehyeon Hwang and Soyun Choi contributed equally to this work.
^*Correspondence: Min‑Suk Song, Sang Jick Kim, Dae‑Hyuk Kweon

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.

논문정보

형식Research article
게재일2025년 01월 (BRIC 등록일 2025-01-27)
연구진국내 연구진
분야 생명과학 > 생물공학

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