The uneven worldwide vaccination coverage against severeacute respiratory syndrome coronavirus 2 (SARS-CoV-2) andemergence of variants escaping immunity call for broadly effectiveand easily deployable therapeutic agents. We have previouslydescribed the human single-chain scFv76 antibody, whichrecognizes SARS-CoV-2 Alpha, Beta, Gamma and Delta variants.We now show that scFv76 also neutralizes the infectivityand fusogenic activity of the Omicron BA.1 and BA.2 variants.Cryoelectron microscopy (cryo-EM) analysis reveals thatscFv76 binds to a well-conserved SARS-CoV-2 spike epitope,providing the structural basis for its broad-spectrum activity.We demonstrate that nebulized scFv76 has therapeutic efficacyin a severe hACE2 transgenic mouse model of coronavirus disease2019 (COVID-19) pneumonia, as shown by body weightand pulmonary viral load data. Counteraction of infection correlateswith inhibition of lung inflammation, as observed byhistopathology and expression of inflammatory cytokines andchemokines. Biomarkers of pulmonary endothelial damagewere also significantly reduced in scFv76-treated mice. The resultssupport use of nebulized scFv76 for COVID-19 inducedby any SARS-CoV-2 variants that have emerged so far.
Spike mutation resilient scFv76 antibody counteracts SARS-CoV-2 lung damage upon aerosol delivery
Antonio Rossi;
2023
Abstract
The uneven worldwide vaccination coverage against severeacute respiratory syndrome coronavirus 2 (SARS-CoV-2) andemergence of variants escaping immunity call for broadly effectiveand easily deployable therapeutic agents. We have previouslydescribed the human single-chain scFv76 antibody, whichrecognizes SARS-CoV-2 Alpha, Beta, Gamma and Delta variants.We now show that scFv76 also neutralizes the infectivityand fusogenic activity of the Omicron BA.1 and BA.2 variants.Cryoelectron microscopy (cryo-EM) analysis reveals thatscFv76 binds to a well-conserved SARS-CoV-2 spike epitope,providing the structural basis for its broad-spectrum activity.We demonstrate that nebulized scFv76 has therapeutic efficacyin a severe hACE2 transgenic mouse model of coronavirus disease2019 (COVID-19) pneumonia, as shown by body weightand pulmonary viral load data. Counteraction of infection correlateswith inhibition of lung inflammation, as observed byhistopathology and expression of inflammatory cytokines andchemokines. Biomarkers of pulmonary endothelial damagewere also significantly reduced in scFv76-treated mice. The resultssupport use of nebulized scFv76 for COVID-19 inducedby any SARS-CoV-2 variants that have emerged so far.| File | Dimensione | Formato | |
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Descrizione: Spike mutation resilient scFv76 antibody counteracts SARS-CoV-2 lung damage upon aerosol delivery
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