Influenza and viral escape
Grant number: 1008854 | Funding period: 2011 - 2014
Introduction of a new influenza strain into human circulation leads to a rapid global spread of the virus (e.g. H1N1-09 pandemic) due to minimal antibody immunity. Established T-cell immunity towards conserved viral regions promotes rapid recovery. However, the protective immunity exerts pressure on influenza, leading to "escape" mutations. We will unravel how the viral mutants emerge and propose strategies for T cell-based protective immunity and vaccine design against influenza.
Related publications (12)
Broad CD8( ) T cell cross-recognition of distinct influenza A strains in humans
Emma J Grant, Tracy M Josephs, Liyen Loh, E Bridie Clemens, Sneha Sant, Mandvi Bharadwaj, Weisan Chen, Jamie Rossjohn, Stephanie Gras, Katherine Kedzierska
Newly-emerged and vaccine-mismatched influenza A viruses (IAVs) result in a rapid global spread of the virus due to minimal antibo..
Lack of Heterologous Cross-reactivity toward HLA-A*02:01 Restricted Viral Epitopes Is Underpinned by Distinct alpha beta T Cell Receptor Signatures
Emma J Grant, Tracy M Josephs, Sophie A Valkenburg, Linda Wooldridge, Margaret Hellard, Jamie Rossjohn, Mandvi Bharadwaj, Katherine Kedzierska, Stephanie Gras
αβT cell receptor (TCR) genetic diversity is outnumbered by the quantity of pathogenic epitopes to be recognized. To provide effic..
A Role of Influenza Virus Exposure History in Determining Pandemic Susceptibility and CD8( ) T Cell Responses
Sergio M Quinones-Parra, E Bridie Clemens, Zhongfang Wang, Hayley A Croom, Lukasz Kedzierski, Jodie McVernon, Dhanasekaran Vijaykrishna, Katherine Kedzierska
UNLABELLED: Novel influenza viruses often cause differential infection patterns across different age groups, an effect that is def..
Establishment of functional influenza virus-specific CDS T cell memory pools after intramuscular immunization
Zhongfang Wang, Brendon Y Chua, Javier Vega Ramos, Sergio M Quinones Parra, Emily Fairmaid, Lorena E Brown, David C Jackson, Katherine Kedzierska
The emergence of the avian-origin influenza H7N9 virus and its pandemic potential has highlighted the ever-present need to develop..
Oseltamivir Prophylaxis Reduces Inflammation and Facilitates Establishment of Cross-Strain Protective T Cell Memory to Influenza Viruses
Nicola L Bird, Matthew R Olson, Aeron C Hurt, Christine M Oshansky, Ding Yuan Oh, Patrick C Reading, Brendon Y Chua, Yilun Sun, Li Tang, Andreas Handel, David C Jackson, Stephen J Turner, Paul G Thomas, Katherine Kedzierska
CD8(+) T cells directed against conserved viral regions elicit broad immunity against distinct influenza viruses, promote rapid vi..
Proinsulin-Specific, HLA-DQ8, and HLA-DQ8-Transdimer-Restricted CD4( ) T Cells Infiltrate Islets in Type 1 Diabetes
Vimukthi Pathiraja, Janine P Kuehlich, Peter D Campbell, Balasubramanian Krishnamurthy, Thomas Loudovaris, P Toby H Coates, Thomas C Brodnicki, Philip J O'Connell, Katherine Kedzierska, Christine Rodda, Philip Bergman, Erin Hill, Anthony W Purcell, Nadine L Dudek, Helen E Thomas, Thomas WH Kay, Stuart I Mannering
Type 1 diabetes (T1D) develops when insulin-secreting β-cells, found in the pancreatic islets of Langerhans, are destroyed by infi..
Preexisting CD8( ) T-cell immunity to the H7N9 influenza A virus varies across ethnicities
Sergio Quinones-Parra, Emma Grant, Liyen Loh, Thi HO Nguyen, Kristy-Anne Campbell, Steven YC Tong, Adrian Miller, Peter C Doherty, Dhanasekaran Vijaykrishna, Jamie Rossjohn, Stephanie Gras, Katherine Kedzierska
The absence of preexisting neutralizing antibodies specific for the novel A (H7N9) influenza virus indicates a lack of prior human..
Acute emergence and reversion of influenza A virus quasispecies within CD8( ) Tcell antigenic peptides
Sophie A Valkenburg, Sergio Quinones-Parra, Stephanie Gras, Naomi Komadina, Jodie McVernon, Zhongfang Wang, Hanim Halim, Pina Iannello, Catherine Cole, Karen Laurie, Anne Kelso, Jamie Rossjohn, Peter C Doherty, Stephen J Turner, Katherine Kedzierska
Influenza A virus-specific CD8(+) cytotoxic T lymphocytes (CTLs) provide a degree of cross-strain protection that is potentially s..
Preemptive priming readily overcomes structure-based mechanisms of virus escape
Sophie A Valkenburg, Stephanie Gras, Carole Guillonneau, Lauren A Hatton, Nicola A Bird, Kelly-Anne Twist, Hanim Halim, David C Jackson, Anthony W Purcell, Stephen J Turner, Peter C Doherty, Jamie Rossjohn, Katherine Kedzierska
A reverse-genetics approach has been used to probe the mechanism underlying immune escape for influenza A virus-specific CD8(+) T ..
Nudeoprotein of influenza A virus is a major target of immunodominant CD8( ) T-cell responses
Emma Grant, Chao Wu, Kok-Fei Chan, Sidonia Eckle, Mandvi Bharadwaj, Quan Ming Zou, Katherine Kedzierska, Weisan Chen
Influenza A virus causes annual epidemics and sporadic pandemics, resulting in significant morbidity and mortality worldwide. Vacc..
Consequences of suboptimal priming are apparent for low-avidity T-cell responses
Vanessa Venturi, Miles P Davenport, Natasha G Swan, Peter C Doherty, Katherine Kedzierska
The emergence of the novel reassortant A(H1N1)-2009 influenza virus highlighted the threat to the global population posed by an in..
Use it or lose it: establishment and persistence of T cell memory
Katherine Kedzierska, Sophie A Valkenburg, Peter C Doherty, Miles P Davenport, Vanessa Venturi
Pre-existing T cell memory provides substantial protection against viral, bacterial, and parasitic infections. The generation of p..