Biology subjects

Deride, C.

Publications and source records attributed to Deride, C..

3 recordsLinked to original sources

bioRxiv2025

A protective bispecific antibody targets both Nipah virus surface glycoproteins and limits viral escape

Nipah virus (NiV) and Hendra virus (HeV) are highly pathogenic henipaviruses without approved human vaccines or therapies. Here, we report on a highly potent bispecific therapeutic that combines an anti-fusion (F) nanobody with an anti-receptor binding protein (RBP) antibody to deliver a dual-targeting biologic that is resistant to viral escape. We show that the nanobody, DS90, engages a unique, conserved site within prefusion F of NiV and HeV, and provides neutralization and complete protection from NiV disease. Bispecific engineering of DS90 with the anti-RBP mAb m102.4 results in neutralization, elimination of viral escape and superior protection from NiV disease compared to leading monovalent approaches. These findings carry implications for the development of cross-neutralizing immunotherapies that limit the emergence of henipaviral escape mutants.

microbiology↗

bioRxiv2024

Novel Library Assembly Technique for Developing Nanobodies Targeting IPNv VP2 Protein

Infectious pancreatic necrosis virus (IPNv) poses a significant threat to the global salmon farming industry, causing high mortality and economic losses. Given the limitations of traditional antibody therapies in aquaculture, we explored the development of nanobodies targeting the VP2 protein of IPNv. We developed a novel nanobody library generation method using a streamlined assembly protocol based on Type IIS restriction enzymes. This method enabled quick and efficient bacterial display library generation, and concatenated, multi-level cloning through an ingenious design in which the ligation of the first level generates a new restriction site that can be utilized in the subsequent cloning level, allowing for rapid transfer to other vectors. By combining this assembly approach with density gradient-based enrichment and high-throughput screening, we identified nanobodies that specifically recognize IPNvs VP2 protein. Notably, the P9 clone demonstrated high specificity for IPNv in immunofluorescence assays, highlighting its diagnostic potential. Our method not only accelerates nanobody library generation but also enhances its quality and adaptability, marking a significant advancement in enhancing the responsiveness of nanobody development platforms against emerging pathogen outbreaks.

molecular biology↗

bioRxiv2020

Fast isolation of sub-nanomolar affinity alpaca nanobody against the Spike RBD of SARS-CoV-2 by combining bacterial display and a simple single-step density gradient selection

Despite unprecedented global efforts to rapidly develop SARS-CoV-2 treatments, in order to reduce the burden placed on health systems, the situation remains critical. Effective diagnosis, treatment, and prophylactic measures are urgently required to meet global demand: recombinant antibodies fulfill these requirements and have marked clinical potential. Here, we describe the fast-tracked development of an alpaca Nanobody specific for the receptor-binding-domain (RBD) of the SARS-CoV-2 Spike protein with therapeutic potential applicability. We present a rapid method for nanobody isolation that includes an optimized immunization regimen coupled with VHH library E. coli surface display, which allows single-step selection of high-affinity nanobodies using a simple density gradient centrifugation of the bacterial library. The selected single and monomeric Nanobody, W25, binds to the SARS-CoV-2 S RBD with sub-nanomolar affinity and efficiently competes with ACE-2 receptor binding. Furthermore, W25 potently neutralizes SARS-CoV-2 wild type and the D614G variant with IC50 values in the nanomolar range, demonstrating its potential as antiviral agent.

molecular biology↗