This project is part of the overarching project 'ACZI – Innovative antibody-based strategies to combat future emergence of zoonotic viral infections'.

Timeline

2019 – 2023

Group and collaboration

Collaboration:
Dr. Berend-Jan Bosch, Dr. Xander de Haan, Prof. Frank van Kuppeveld, Prof. Andrea Grone, Dr. Esther Nolte ‘t Hoen, Dr. Christine Jansen – Dept. Veterinary Medicine, Utrecht University
Dr. Bart Haagmans, Dr. Barry Rockx, Dr. Bas Oude Munnink, Prof. Ron Fouchier, Prof. Marion Koopmans – Dept. Viroscience, Erasmus MC

PhD student: Anna Mykytyn

Project description

Broadly reactive nanobodies targeting conserved sites on the coronavirus spike protein will be induced following a sequential immunization of camelids with heterologous spike proteins. In parallel, B-cells from MERS-CoV patients will be immortalized using Epstein Barr virus or a lentivirus transducing BCL6 and BCXL. As antigens, we will use trimeric spike ectodomains of related human-infecting betacoronaviruses (MERS-CoV, SARS-CoV, HCoV-OC43 and HCoV-HKU1), by means of expression methodology that we employed previously to solve prefusion spike structures of several coronaviruses. Nanobodies will be isolated using recently established techniques and purified nanobodies will be analyzed for their cross-reactivity against the spike proteins of a broad panel of coronaviruses.

Tasks

• Isolation of broadly reactive CoV spike antibodies
• Characterization of broadly reactive antibodies
• Protection efficacy of broad-range antibodies against coronaviruses