Poster Presentation The Australasian Society for Immunology 2017 Annual Scientific Meeting

Novel CD8+ T-cell targets for protection of Indigenous Australians against severe influenza disease (#250)

Luca Hensen 1 , Patricia Illing 2 , Nicole Mifsud 2 , Marios Koutsakos 1 , Oanh Nguyen 1 , Stephanie Gras 2 , Adrian Miller 3 , Jamie Rossjohn 2 , Steve Rockman 4 , Anthony Purcell 2 , Steven Tong 1 5 , Bridie Clemens 1 , Katherine Kedzierska 1
  1. Department of Microbiology and Immunology, University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Parkville, Victoria, Australia
  2. Infection and Immunity Program, Monash Biomedicine Discovery Institute and Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, Australia
  3. Office of the Pro Vice-Chancellor Indigenous Leadership, Charles Darwin University, Darwin, Northern Territory, Australia
  4. Seqirus, Parkville, Victoria, Australia
  5. Menzies School of Health Research, Casuarina, Northern Territory, Australia

Indigenous Australians are highly susceptible to seasonal as well as pandemic influenza viruses. During the 2009 H1N1 pandemic, Indigenous Australians accounted for 16% of hospitalized patients, while they only comprise 2.5% of the Australian population. The underlying mechanism for such increased morbidity and mortality in Indigenous Australians is still unclear and the effectiveness of current antibody-based seasonal influenza vaccines in this population is not well understood. A broadly cross-reactive CD8+ T-cell vaccine could provide Indigenous Australians with protection against seasonal as well as pandemic influenza viruses. As T-cell responses are restricted by HLA allele expression, which varies greatly across ethnicities, T-cell vaccines may need to be population specific. Therefore, it is necessary to identify the particular influenza peptide targets presented by HLA alleles predominant in Indigenous Australians and assess their immunogenicity. We established a panel of C1R cells expressing the 6 most frequent HLA alleles in Indigenous Australians, namely A*34:01, A*24:02, A*11:01, B*56:01, B*13:01 and B*15:21. A CD8+ T-cell activating vaccine, including conserved peptides for all six of these HLA alleles could be protective for ~80% of Indigenous Australians. The influenza peptide repertoire presented by each of these HLA alleles can then be determined by infecting the C1R cell lines with influenza A and B viruses, purifying the presented peptide antigens and identifying them by mass spectrometry. A time course study of A*24:02-expressing C1R cells infected with influenza B (B/Malaysia/2506/04) identified 39 presented peptides derived from 9 proteins of the virus of which 50% are more than 90% conserved across all influenza B strains. These peptides were screened for immunogenic potential in A*24:02-expressing mice and A*24:02+ Indigenous Australians. Overall, these studies will provide the first in-depth analysis of HLAs dominant in Indigenous populations in Australia and elsewhere, and their protective peptide repertoire.