Eco-evolutionary dynamics of pathogen immune-escape: deriving a population-level phylodynamic curve

Journal of The Royal Society Interface, Год журнала: 2025, Номер 22(225)

Опубликована: Апрель 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.

Язык: Английский

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

Molecular Medicine, Год журнала: 2025, Номер 31(1)

Опубликована: Апрель 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.

Язык: Английский

SARS-CoV-2 Variant-Specific Antibodies in Vaccinated Inflammatory Bowel Disease Patients

Vaccines, Год журнала: 2025, Номер 13(6), С. 595 - 595

Опубликована: Май 30, 2025

Background/Objectives: Patients suffering from inflammatory bowel diseases (IBDs) undergoing treatment with anti-TNF antibodies mount a diminished humoral immune response to vaccination against SARS-CoV-2 compared healthy controls. The characterization of variant-specific responses is particularly warranted among immunosuppressed patients, where reduced may necessitate further medical interventions. Methods: This pilot study investigated the vaccinated IBD patients on medication and comparable group individuals viral variants Alpha, Beta, Gamma, Delta, Omicron BA.1 BA.5. While total IgG targeting receptor binding site spike protein were quantified using chemiluminescence microparticle immunoassay (CMIA), their potential neutralizing capacity was determined commercial in-house surrogate virus neutralization tests (sVNTs) VSV-pseudotyped test (pVNT) as gold standard. Results: Employing assays recapitulated escape functions variants. Conspicuously, antibody reactivity Alpha BA.5 strikingly poor in patient sera post-initial individuals. A comparison diagnostic performance pVNT revealed that identification inadequate by CMIA sVNT require adjustments cut-off values end-point titration sera. Following adaptation values, exhibited all tested assay panel used substantiated impact therapy strength, function, breadth several measured following second observed first vaccination. Conclusion: Variant-specific sVNTs pVNTs have serve valuable tools for evaluating efficacy adapted vaccines inform clinical interventions care patients. Anti-TNF-treated levels below optimized threshold should be considered early booster and/or close immunological monitoring.

Язык: Английский