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Updated: Jan 23, 2026

Author Spotlight: A Pseudotype Virus System for Assessing Omicron Subvariants and Neutralizing Antibodies in SARS-CoV-2 Research

Author Spotlight: A Pseudotype Virus System for Assessing Omicron Subvariants and Neutralizing Antibodies in SARS-CoV-2 Research

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Ingeniería de nanopartículas basadas en péptidos similares a la elastina que muestran el dominio variable de la

Duc H T Le^1,2, Jenny van Oostrum², Els van de Westerlo²

¹Department of Biomedical Engineering, Institute for Complex Molecular Systems (ICMS), Eindhoven University of Technology, Eindhoven 5600 MB, The Netherlands.

Biomacromolecules

|January 21, 2026

Abstract:

Elastin-like polypeptides (ELPs) are self-assembling recombinant biopolymers that can be precisely engineered to display functional targeting ligands. In this study, we developed ELP-based nanoparticles (NPs) displaying the variable domain of the heavy chain of heavy-chain-only antibodies (VHHs) targeting the SARS-CoV-2 spike protein. By tuning VHH selection, multivalency, and surface display density, we created targeted ELP NPs capable of blocking entry of spike-protein-presenting virus-like particles (VLPs) and live viruses, with subnanomolar IC₅₀ values, significantly outperforming the monovalent VHH equivalents. Notably, optimizing multivalency and VHH density unlocked broad virus-neutralizing potency against multiple variants, including Omicron variants resistant against the monovalent VHH equivalents. Confocal imaging further revealed that VHH-ELP NPs formed aggregates with VLPs, enhancing uptake by M1 macrophages, suggesting potential for eliciting vaccinal effects. Overall, this work highlights the versatility of ELP NPs as a tunable antiviral platform and provides design principles for next-generation nanotherapeutics against evolving viral threats.

Palabras clave:

nanopartículas péptidos similares a la elastina anticuerpos de cadena pesada únicamente SARS-CoV-2 neutralización viral vacunas

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