Abstract: FR-PO015
Neutralization of the Omicron Variant of SARS-CoV-2 Is Effective by a Human and a Mouse Soluble ACE2 Protein
Session Information
- COVID-19: AKI Outcomes, Biomarkers, Treatments, Case Reports
November 04, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
Abstract Time: 10:00 AM - 12:00 PM
Category: Coronavirus (COVID-19)
- 000 Coronavirus (COVID-19)
Authors
- Hassler, Luise, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
- Nicolaescu, Vlad I., The University of Chicago, Chicago, Illinois, United States
- Wysocki, Jan, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
- Randall, Glenn, The University of Chicago, Chicago, Illinois, United States
- Batlle, Daniel, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
Background
We have previously reported that ACE2 618-DDC-ABD, a soluble ACE2 protein with extended duration of action and increased binding affinity for SARS-CoV-2, provides lung and kidney protection in a lethal mouse model of SARS-CoV-2 infection. Moreover, we showed that this protein also neutralizes the gamma and delta variant SARS-CoV-2 infection in Vero E6 cells. As omicron is most prevalent SARS-CoV-2 variant we tested whether ACE2 618-DDC-ABD can also neutralize this variant and hypothesized that it is more sensitive to mouse ACE2 as well as human ACE2.
Methods
The omicron BA.1 SARS-CoV-2 strain was incubated with various concentrations of ACE2 618-DDC-ABD (0-180ug/ml) for 1 hour at 37°C. Human ACE2 1-740 and mouse ACE2 1-740 were used as controls at the same concentrations. These mixtures were then used to infect Vero E6 cells. Cells were allowed to grow for 3-4 days until a noticeable cytopathic effect was observed in control wells (0μg/ml soluble ACE2 proteins). Cell numbers were assessed by staining cells with crystal violet and reading absorbance of each well at 595 nm. Values were then normalized to the 0μg/ml control and expressed as a percentage of the mock (no virus) control wells.
Results
ACE2 618-DDC-ABD (red) neutralized the omicron BA.1 variant at all concentrations tested and to a similar extent as native human soluble ACE2 1-740 (blue) used as control. Native mouse ACE2 1-740 (black) also neutralized infection completely at high concentrations while lower concentrations were less effective as compared to low concentrations of ACE2 618-DDC-ABD or human ACE2 1-740.
Conclusion
Soluble ACE2 618-DDC-ABD effectively neutralizes the omicron BA.1 variant of SARS-CoV-2 in Vero E6 cells at concentrations lower than those we have previously shown are required for gamma, delta and wildtype SARS-CoV-2. Moreover, the omicron BA.1 variant is sensitive to neutralization by soluble mouse ACE2.
Funding
- NIDDK Support