Mol Ther . Human inhalable antibody fragments neutralizing SARS-CoV-2 variants for COVID-19 therapy

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Mol Ther


. 2022 Feb 12;S1525-0016(22)00096-X.
doi: 10.1016/j.ymthe.2022.02.013. Online ahead of print.
Human inhalable antibody fragments neutralizing SARS-CoV-2 variants for COVID-19 therapy


Olga Minenkova ¹ , Daniela Santapaola ¹ , Ferdinando Maria Milazzo ¹ , Anna Maria Anastasi ¹ , Gianfranco Battistuzzi ¹ , Caterina Chiapparino ¹ , Antonio Rosi ¹ , Giuseppe Gritti ² , Gianmaria Borleri ² , Alessandro Rambaldi ³ , Clélia Dental ⁴ , Cécile Viollet ⁴ , Bruno Pagano ⁵ , Laura Salvini ⁶ , Emanuele Marra ⁷ , Laura Luberto ⁷ , Antonio Rossi ⁸ , Anna Riccio ⁹ , Emilio Merlo Pich ¹ , Maria Gabriella Santoro ¹⁰ , Rita De Santis ¹¹



Affiliations

• PMID: 35167974
• DOI: 10.1016/j.ymthe.2022.02.013

Abstract

As of December 2021, coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), remains global emergency and novel therapeutics are urgently needed. Here we describe human single chain variable fragment (scFv) antibodies (76clAbs) that block an epitope of the SARS-CoV-2 spike protein essential for ACE2-mediated entry into cells. 76clAbs neutralize the delta variant and other variants being monitored (VBMs) and inhibit spike-mediated pulmonary cell-cell fusion, a critical feature of COVID-19 pathology. In two independent animal models, intranasal administration counteracted the infection. Due to high efficiency, remarkable stability, resilience to nebulization and low cost of production, 76clAbs may become a relevant tool for rapid, self-administrable early intervention in SARS-CoV-2-infected subjects independently of their immune status.