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

• Published in: Molecular therapy Vol. 30; no. 5; pp. 1979 - 1993
• Main Authors: Minenkova, Olga, Santapaola, Daniela, Milazzo, Ferdinando Maria, Anastasi, Anna Maria, Battistuzzi, Gianfranco, Chiapparino, Caterina, Rosi, Antonio, Gritti, Giuseppe, Borleri, Gianmaria, Rambaldi, Alessandro, Dental, Clélia, Viollet, Cécile, Pagano, Bruno, Salvini, Laura, Marra, Emanuele, Luberto, Laura, Rossi, Antonio, Riccio, Anna, Merlo Pich, Emilio, Santoro, Maria Gabriella, De Santis, Rita
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 04.05.2022; American Society of Gene & Cell Therapy
• Subjects: aerosol therapy; Animals; anti-COVID-19 antibody; Antibodies, Neutralizing - therapeutic use; Antibodies, Viral - therapeutic use; COVID-19; COVID-19 pandemic; COVID-19 therapy; human single-chain antibody; Humans; Immunoglobulin Fragments; inhalation; intranasal administration; Original; phage display; SARS-CoV-2 - genetics; SARS-CoV-2 variant neutralization; Spike Glycoprotein, Coronavirus; SARS-CoV-2 variant neutralization; inhalation; COVID-19 pandemic; anti-COVID-19 antibody; aerosol therapy; intranasal administration; phage display; COVID-19 therapy; human single-chain antibody
• ISSN: 1525-0016; 1525-0024
• DOI: 10.1016/j.ymthe.2022.02.013

As of December 2021, coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), remains a 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. Because of their 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. [Display omitted] De Santis and colleagues describe engineered human antibody fragments (scFvs), which are extremely effective at neutralizing SARS-CoV-2 variants. Because of their high stability and efficacy in preclinical models, intranasal or aerosol delivery of scFv antibodies represents a promising approach for halting SARS-CoV-2 infection at an early stage regardless of vaccination status.