Human Monoclonal Antibodies to monitor Antigenic Drift in Influenza Virus
Supervisors: Prof Alain Townsend and Dr Pramila Rijal
Influenza virus incorporates frequent mutations in its genome (antigenic drift) via which the virus defies the host antibody response, requiring update of the seasonal vaccine regularly. WHO Influenza Collaborating Centres select a vaccine strain for every season, based on the evolving viral sequences and antigenicity for ferrets. Ferret antisera raised to selected viruses are tested for neutralization and haemagglutination inhibition (HI) to define the antigenic relatedness of newly emerging strains. However, ferret antisera behave differently from human sera sometimes, and there is a need for improved methods for vaccine strain selection.
We have shown that human monoclonal antibodies, isolated from vaccinated or infected donors, can be used as tools to recapitulate antigenic drift in vitro (Huang et al 2015). This would provide additional information to existing methods for the selection of seasonal vaccine virus, and may be able to predict the course of viral evolution.
The project will involve isolation of human monoclonal antibodies from vaccinated and infected donors, and use them along with additional antibodies isolated by our collaborators in Taiwan and China to study antigenic drift in circulating seasonal H1N1 and H3N2 influenza viruses. We will also look at the sera from different age cohorts to identify the dominant focused immune responses to certain epitopes in the population.
This is a collaborative project with the Crick Worldwide Influenza Centre, where we aim to develop panels of informative antibodies that can be distributed to the WHO Collaborative Centres around the world to compare with the standard ferret antisera.
The student will learn and gain experience in single cell sorting by FACS, PCR and cloning of genes, antibody expression and purification and testing by immunofluorescence, ELISA, neutralisation and haemagglutinin inhibition assays.