Identification of influenza escape mutants in the context of T-cell mediated vaccination MB Bull1, 2, HG Gu2, DKW Chu2, LLM Poon2 and SA Valkenburg1,2 1HKU Pasteur Research Pole, The University of Hong Kong, Pokfulam, Hong Kong; 2WHO Collaborating Centre for Infectious Disease Epidemiology and Control, School of Public Health, The University of Hong Kong, Pokfulam, Hong Kong
Influenza is a constant threat to public health and significant measures have been taken to prepare for the potential emergence of a novel pandemic strain. When viruses cross the species barrier it can introduce highly pathogenic strains into the human population, as seen with avian influenza. Existing avian strains have a high rate of mortality in humans but have not genetically adapted to be highly transmissible, a possibility that is a major threat to human health. Current influenza vaccination strategies endeavor to protect the public from seasonal and pandemic strains by inducing an immunological response to surface antigens which are susceptible to seasonal antigenic drift and potential pandemic shift. Improved approaches to influenza vaccine development include priming T cells to conserved viral epitopes which may confer cross-clade universal protection against novel strains. However, as influenza viruses have already shown anti-viral resistance and antigenic drift, immune escape from vaccine mediated T cell immunity may also occur. This project investigates if a universal T cell activating vaccine increases the rate of mutation within both CD4+ and CD8+ epitopes across the influenza genome. Viral RNA is extracted from the lungs of infected mice, of differing vaccination status. The whole influenza virus genome is then amplified and analysed using Next Generation Sequencing. Preliminary results have shown that there is an increased rate of single nucleotide polymorphisms (SNPs) across the influenza genome in mice which have received a T cell priming vaccine. Additionally the shotgun metagenomic sequencing data has highlighted mutated regions that may contain novel T cell influenza epitopes. Results from this study have highlighted that immune pressure can be enhanced by universal vaccines, leading to increased SNPs, which could occur within potential T cell epitope regions. These findings should be taken into consideration to help inform future vaccine strategy and design.
Funding: This project is funded by Hong Kong Research Grants Council.