Our research centers around the influenza neuraminidase protein as a promising target for therapeutic interventions, including antibodies, drugs, and vaccines.
Research
Improving Antibody Efficacy In Vitro and In Silico
We have extensive experience in the discovery and characterization of monoclonal antibodies (mAbs) targeting glycoproteins of infectious disease viruses. Over the years, we have discovered several broadly reactive mAbs effective against viruses from different clades and subtypes. These antibodies target conserved epitopes. Despite the broad reactivity of these antibodies, viruses can still evade their effects by mutating the key anchor epitopes or the secondary, less conserved contact residues on the periphery.
Our goal is to mature the antibodies in vitro to keep pace with virus evolution. We propose leveraging structural data, employing in vitro affinity maturation methods, and utilizing artificial intelligence (AI) designs to maintain and enhance antibody effectiveness. To achieve this, we collaborate with structural biology groups and Antibody AI companies.
Vaccine targeting Influenza Neuraminidase
Traditional influenza vaccines are primarily based on the haemagglutinin (HA) protein, which undergoes rapid evolution, necessitating frequent updates. By comparison, neuraminidase (NA) undergoes less antigenic evolution and antibodies to NA are effective against evolved viruses for many years. By focusing on the NA protein, we aim to develop vaccines with longer-lasting protection against antigenic drift variants, with a particular emphasis on H5N1 pandemic preparedness.
The experience gained from studying neuraminidase proteins is further applied to the discovery of novel influenza drugs through collaborative projects.
Our Team
-
Pramila Rijal
Career Development Fellow
Collaborators
Professor Kuan-Ying Arthur Huang, National Taiwan University, Taiwan
Professor Yan Wu, Beijing Institutes of Life Science, China
Professor Thomas Bowden, University of Oxford, UK
Professor Elma Tchilian, The Pirbright Institute, UK
Dr. Darwyn Kobasa, University of Manitoba, Canada
Professor Erica Ollmann Saphire, La Jolla Institute for Immunology, USA
Professor Mark Howarth, University of Cambridge, UK