健康な人は、ウイルスとその亜種に対抗する抗体の供給源となりうる Healthy humans can be a source of antibodies countering the virus and its variants
2022-08-30 アメリカ・ロスアラモス国立研究所(LANL)
SARS-CoV-1とSARS-CoV-2を区別できるように、特異的な結合特性を持つ抗体と、両方のウイルスを認識する抗体を同定するために、選択とスクリーニングのプロセスを最適化した。この戦略により、非常に多様なセットを手に入れることができた。
開発した抗体探索法は、SARS-CoV-2ウイルスの前例のない数の領域を認識する抗体の豊富なレパートリーを独自に作り出した、と筆頭著者Lilloは述べている。このような特性をもつ抗体は、病原体を特異的に認識するためにも、治療用抗体カクテルを開発するためにも必要である。抗体カクテルは、単一の抗体よりも、病原体の自然な変異傾向にもかかわらず、その機能を維持する可能性が高い。
追跡調査(原稿作成中)により、我々の研究で見つかった最も優れた抗体の1つである抗体F07が、SARS-CoV-2のオリジナル株だけでなく、DeltaとOmicronも認識することがわかった。
<関連情報>
- https://discover.lanl.gov/news/0829-covid-19-virus-detection
- https://www.tandfonline.com/doi/full/10.1080/21655979.2022.2076390
健康なヒトはCOVID-19に対抗する抗体の供給源となりうる Healthy humans can be a source of antibodies countering COVID-19
Nileena Velappan,Hau B. Nguyen,Sofiya Micheva-Viteva,Daniel Bedinger,Chunyan Ye,Betty Mangadu,Austin J. Watts,Robert Meagher,Steven Bradfute,Bin Hu,Geoffrey S. Waldo & Antonietta M. Lillo
Bioengineered Published: 21 May 2022
DOI:https://doi.org/10.1080/21655979.2022.2076390
ABSTRACT
Here, we describe the isolation of 18 unique anti SARS-CoV-2 human single-chain antibodies from an antibody library derived from healthy donors. The selection used a combination of phage and yeast display technologies and included counter-selection strategies meant to direct the selection of the receptor-binding motif (RBM) of SARS-CoV-2 spike protein’s receptor binding domain (RBD2). Selected antibodies were characterized in various formats including IgG, using flow cytometry, ELISA, high throughput SPR, and fluorescence microscopy. We report antibodies’ RBD2 recognition specificity, binding affinity, and epitope diversity, as well as ability to block RBD2 binding to the human receptor angiotensin-converting enzyme 2 (ACE2) and to neutralize authentic SARS-CoV-2 virus infection in vitro. We present evidence supporting that: 1) most of our antibodies (16 out of 18) selectively recognize RBD2; 2) the best performing 8 antibodies target eight different epitopes of RBD2; 3) one of the pairs tested in sandwich assays detects RBD2 with sub-picomolar sensitivity; and 4) two antibody pairs inhibit SARS-CoV-2 infection at low nanomolar half neutralization titers. Based on these results, we conclude that our antibodies have high potential for therapeutic and diagnostic applications. Importantly, our results indicate that readily available non immune (naïve) antibody libraries obtained from healthy donors can be used to select high-quality monoclonal antibodies, bypassing the need for blood of infected patients, and offering a widely accessible and low-cost alternative to more sophisticated and expensive antibody selection approaches (e.g. single B cell analysis and natural evolution in humanized mice).
