An engineered miniACE2 protein secreted by mesenchymal stromal cells effectively neutralizes multiple SARS-CoV- 2 variants in vitro DOI Creative Commons

Sara Moreno-Jiménez,

Gina López-Cantillo,

Jenny Andrea Arévalo-Romero

et al.

Molecular Medicine, Journal Year: 2025, Volume and Issue: 31(1)

Published: April 23, 2025

Abstract SARS-CoV- 2 continues to evolve, producing novel Omicron subvariants through recombinant lineages that acquire new mutations, undermining existing antiviral strategies. The viral fitness and adaptive potential of present significant challenges emergency treatments, particularly monoclonal antibodies, which demonstrate reduced efficacy with the emergence each variant. Consequently, immunocompromised individuals, who are more susceptible severe manifestations COVID- 19 face heightened risks critical complications mortality, remain vulnerable in absence effective treatments. To develop translational approaches can benefit this at-risk population establish broader therapeutic strategies applicable across variants, we previously designed engineered silico miniACE2 decoys (designated BP2, BP9, BP11). These demonstrated promising neutralizing subvariants. In study, leveraged mesenchymal stromal cells (MSCs) for tissue repair immunomodulation lung injuries used these as a platform secretion BP2. Our innovative assays, were conducted BP2 protein secreted into culture supernatant BP2-MSCs, 2, including development advanced platforms holds promise scalability effectively mitigate impact 19, contributing resilient treatment against evolving landscape variants.

Language: Английский

Eco-evolutionary dynamics of pathogen immune-escape: deriving a population-level phylodynamic curve DOI Creative Commons
Bjarke Frost Nielsen, Chadi M. Saad-Roy, C. Jessica E. Metcalf

et al.

Journal of The Royal Society Interface, Journal Year: 2025, Volume and Issue: 22(225)

Published: April 1, 2025

The phylodynamic curve (Grenfell et al . 2004 Science 303 , 327–332 (doi: 10.1126/science.1090727 )) conceptualizes how immunity shapes the rate of viral adaptation in a non-monotonic fashion, through its opposing effects on abundance and strength selection. However, concrete quantitative model realizations this influential concept are rare. Here, we present an analytic, stochastic framework which population-scale emerges dynamically, allowing us to address questions regarding risk timing emergence immune escape variants. We explore pathogen- population-specific parameters such as immunity, transmissibility, seasonality antigenic constraints affect risk. For pathogens exhibiting pronounced seasonality, find that likely immune-escape variant depends level case importation between regions. Motivated by COVID-19 pandemic, probe non-pharmaceutical interventions (NPIs), lifting thereof, emergence. Looking ahead, has potential become useful tool for probing natural well choices vaccine design distribution implementation NPIs, evolution common pathogens.

Language: Английский

Citations

0
An engineered miniACE2 protein secreted by mesenchymal stromal cells effectively neutralizes multiple SARS-CoV- 2 variants in vitro DOI Creative Commons

Sara Moreno-Jiménez,

Gina López-Cantillo,

Jenny Andrea Arévalo-Romero

et al.

Molecular Medicine, Journal Year: 2025, Volume and Issue: 31(1)

Published: April 23, 2025

Abstract SARS-CoV- 2 continues to evolve, producing novel Omicron subvariants through recombinant lineages that acquire new mutations, undermining existing antiviral strategies. The viral fitness and adaptive potential of present significant challenges emergency treatments, particularly monoclonal antibodies, which demonstrate reduced efficacy with the emergence each variant. Consequently, immunocompromised individuals, who are more susceptible severe manifestations COVID- 19 face heightened risks critical complications mortality, remain vulnerable in absence effective treatments. To develop translational approaches can benefit this at-risk population establish broader therapeutic strategies applicable across variants, we previously designed engineered silico miniACE2 decoys (designated BP2, BP9, BP11). These demonstrated promising neutralizing subvariants. In study, leveraged mesenchymal stromal cells (MSCs) for tissue repair immunomodulation lung injuries used these as a platform secretion BP2. Our innovative assays, were conducted BP2 protein secreted into culture supernatant BP2-MSCs, 2, including development advanced platforms holds promise scalability effectively mitigate impact 19, contributing resilient treatment against evolving landscape variants.

Language: Английский

Citations

0