UNDERSTANDING UNIVERSAL IMMUNITY TO INFLUENZA VIRUSES
Grant number: 1102792 | Funding period: 2016 - 2020
A/Prof Kedzierska’s work combines cutting-edge basic research with unique clinical studies to define how to generate protective immunity against the pandemic and newly emerged influenza viruses. This research will identify key factors that drive the severe and fatal influenza disease in high-risk groups, including the young, elderly, pregnant women and Indigenous Austraians. Findings on the optimal human immunity to influenza viruses will be applicable to other infectious diseases and cancers.
Related publications (42)
Immunization with inactivated whole virus particle influenza virus vaccines improves the humoral response landscape in cynomolgus macaques
Brendon Y Chua, Toshiki Sekiya, Marios Koutsakos, Naoki Nomura, Louise C Rowntree, Thi HO Nguyen, Hayley A McQuilten, Marumi Ohno, Yuki Ohara, Tomohiro Nishimura, Masafumi Endo, Yasushi Itoh, Jennifer R Habel, Kevin J Selva, Adam K Wheatley, Bruce D Wines, P Mark Hogarth, Stephen J Kent, Amy W Chung, David C Jackson
Although antibody-inducing split virus vaccines (SV) are currently the most effective way to combat seasonal influenza, their effi..
T Cell Epitope Discovery in the Context of Distinct and Unique Indigenous HLA Profiles
Luca Hensen, Patricia T Illing, Louise C Rowntree, Jane Davies, Adrian Miller, Steven YC Tong, Jennifer R Habel, Carolien E van de Sandt, Katie L Flanagan, Anthony W Purcell, Katherine Kedzierska, E Bridie Clemens
CD8+ T cells are a pivotal part of the immune response to viruses, playing a key role in disease outcome and providing long-lastin..
Evaluation of Human Circulating T Follicular Helper Cells in Influenza- and SARS-CoV-2-Specific B Cell Immunity.
Marios Koutsakos, Katherine Kedzierska, Thi HO Nguyen
Generation of effective immune protection against viral infection and vaccination depends greatly on a successful engagement and s..
Robust and prototypical immune responses toward influenza vaccines in the high-risk group of Indigenous Australians
Luca Hensen, Thi HO Nguyen, Louise C Rowntree, Timon Damelang, Marios Koutsakos, Malet Aban, Aeron Hurt, Kim L Harland, Maria Auladell, Carolien E van de Sandt, Anngie Everitt, Cath Blacker, Damian A Oyong, Jessica R Loughland, Jessica R Webb, Bruce D Wines, P Mark Hogarth, Katie L Flanagan, Magdalena Plebanski, Adam Wheatley
Morbidity and mortality rates from seasonal and pandemic influenza occur disproportionately in high-risk groups, including Indigen..
Immune cellular networks underlying recovery from influenza virus infection in acute hospitalized patients
Thi HO Nguyen, Marios Koutsakos, Carolien E van de Sandt, Jeremy Chase Crawford, Liyen Loh, Sneha Sant, Ludivine Grzelak, Emma K Allen, Tim Brahm, E Bridie Clemens, Maria Auladell, Luca Hensen, Zhongfang Wang, Simone Nussing, Xiaoxiao Jia, Patrick Gunther, Adam K Wheatley, Stephen J Kent, Malet Aban, Yi-Mo Deng
How innate and adaptive immune responses work in concert to resolve influenza disease is yet to be fully investigated in one singl..
Systems serology detects functionally distinct coronavirus antibody features in children and elderly
Kevin J Selva, Carolien E van de Sandt, Melissa M Lemke, Christina Y Lee, Suzanne K Shoffner, Brendon Y Chua, Samantha K Davis, Thi HO Nguyen, Louise C Rowntree, Luca Hensen, Marios Koutsakos, Chinn Yi Wong, Francesca Mordant, David C Jackson, Katie L Flanagan, Jane Crowe, Shidan Tosif, Melanie R Neeland, Philip Sutton, Paul Licciardi
The hallmarks of COVID-19 are higher pathogenicity and mortality in the elderly compared to children. Examining baseline SARS-CoV-..
TLR2-mediated activation of innate responses in the upper airways confers antiviral protection of the lungs
Georgia Deliyannis, Chinn Yi Wong, Hayley A McQuilten, Annabell Bachem, Michele Clarke, Xiaoxiao Jia, Kylie Horrocks, Weiguang Zeng, Jason Girkin, Nichollas E Scott, Sarah L Londrigan, Patrick C Reading, Nathan W Bartlett, Katherine Kedzierska, Lorena E Brown, Francesca Mercuri, Christophe Demaison, David C Jackson, Brendon Y Chua
The impact of respiratory virus infections on global health is felt not just during a pandemic, but endemic seasonal infections po..
Robust correlations across six SARS-CoV-2 serology assays detecting distinct antibody features
Louise C Rowntree, Brendon Y Chua, Suellen Nicholson, Marios Koutsakos, Luca Hensen, Celia Douros, Kevin Selva, Francesca L Mordant, Chinn Yi Wong, Jennifer R Habel, Wuji Zhang, Xiaoxiao Jia, Lily Allen, Denise L Doolan, David C Jackson, Adam K Wheatley, Stephen J Kent, Fatima Amanat, Florian Krammer, Kanta Subbarao
OBJECTIVES: As the world transitions into a new era of the COVID-19 pandemic in which vaccines become available, there is an incre..
Immune responses to SARS-CoV-2 in three children of parents with symptomatic COVID-19
Shidan Tosif, Melanie R Neeland, Philip Sutton, Paul V Licciardi, Sohinee Sarkar, Kevin J Selva, Anh Ha Do Lien, Celeste Donato, Zheng Quan Toh, Rachel Higgins, Carolien Van de Sandt, Melissa M Lemke, Christina Y Lee, Suzanne K Shoffner, Katie L Flanagan, Kelly B Arnold, Francesca L Mordant, Kim Mulholland, Julie Bines, Kate Dohle
Compared to adults, children with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have predominantly mild or asymptom..
Viral burden, inflammatory milieu and CD8( )T-cell responses to influenza virus in a second-generation thiazolide (RM-5061) and oseltamivir combination therapy study
Simone Nuessing, Edin Mifsud, Luca Hensen, Marios Koutsakos, Zhongfang Wang, Lukasz Kedzierski, Francesca Mercuri, Jean-Francois Rossignol, Aeron C Hurt, Katherine Kedzierska
BACKGROUND: Influenza viruses cause significant morbidity and mortality, especially in young children, elderly, pregnant women and..
Suboptimal SARS-CoV-2-specific CD8( ) T cell response associated with the prominent HLA-A*02:01 phenotype
Jennifer R Habel, Thi HO Nguyen, Carolien E van de Sandt, Jennifer A Juno, Priyanka Chaurasia, Kathleen Wragg, Marios Koutsakos, Luca Hensen, Xiaoxiao Jia, Brendon Chua, Wuji Zhang, Hyon-Xhi Tan, Katie L Flanagan, Denise L Doolan, Joseph Torresi, Weisan Chen, Linda M Wakim, Allen C Cheng, Peter C Doherty, Jan Petersen
An improved understanding of human T cell-mediated immunity in COVID-19 is important for optimizing therapeutic and vaccine strate..
A Shared TCR Bias toward an Immunogenic EBV Epitope Dominates in HLA-B*07:02-Expressing Individuals
Louise C Rowntree, Thi HO Nguyen, Carine Farenc, Hanim Halim, Luca Hensen, Jamie Rossjohn, Tom C Kotsimbos, Anthony W Purcell, Katherine Kedzierska, Stephanie Gras, Nicole A Mifsud
EBV is one of the most common viruses found in humans and is prototypic of a persistent viral infection characterized by periods o..
Immune profiling of influenza-specific B- and T-cell responses in macaques using flow cytometry-based assays
Marios Koutsakos, Toshiki Sekiya, Brendon Y Chua, Hoang Oanh Nguyen Thi, Adam K Wheatley, Jennifer A Juno, Marumi Ohno, Naoki Nomura, Yuki Ohara, Tomohiro Nishimura, Masafumi Endo, Saori Suzuki, Hirohito Ishigaki, Misako Nakayama, Cong T Nguyen, Yasushi Itoh, Masashi Shingai, Kazumasa Ogasawara, Yoichiro Kino, Stephen J Kent
Influenza remains a significant global public health burden, despite substantial annual vaccination efforts against circulating vi..
Metabolic characteristics of CD8( ) T cell subsets in young and aged individuals are not predictive of functionality
Kylie M Quinn, Tabinda Hussain, Felix Kraus, Luke E Formosa, Wai K Lam, Michael J Dagley, Eleanor C Saunders, Lisa M Assmus, Erica Wynne-Jones, Liyen Loh, Carolien E van de Sandt, Lucy Cooper, Kim L Good-Jacobson, Katherine Kedzierska, Laura K Mackay, Malcolm J McConville, Georg Ramm, Michael T Ryan, Nicole L La Gruta
Virtual memory T (TVM) cells are antigen-naïve CD8+ T cells that exist in a semi-differentiated state and exhibit marked prolifera..
Adoptive cellular therapy with T cells expressing the dendritic cell growth factor Flt3L drives epitope spreading and antitumor immunity
Junyun Lai, Sherly Mardiana, Imran G House, Kevin Sek, Melissa A Henderson, Lauren Giuffrida, Amanda XY Chen, Kirsten L Todd, Emma Petley, Jack D Chan, Emma M Carrington, Andrew M Lew, Benjamin J Solomon, Joseph A Trapani, Katherine Kedzierska, Maximilien Evrard, Stephin J Vervoort, Jason Waithman, Phillip K Darcy, Paul A Beavis
Adoptive cell therapies using genetically engineered T cell receptor or chimeric antigen receptor T cells are emerging forms of im..
A serological assay to detect SARS-CoV-2 seroconversion in humans
Fatima Amanat, Daniel Stadlbauer, Shirin Strohmeier, Thi HO Nguyen, Veronika Chromikova, Meagan McMahon, Kaijun Jiang, Guha Asthagiri Arunkumar, Denise Jurczyszak, Jose Polanco, Maria Bermudez-Gonzalez, Giulio Kleiner, Teresa Aydillo, Lisa Miorin, Daniel S Fierer, Luz Amarilis Lugo, Erna Milunka Kojic, Jonathan Stoever, Sean TH Liu, Charlotte Cunningham-Rundles
Here, we describe a serological enzyme-linked immunosorbent assay for the screening and identification of human SARS-CoV-2 serocon..
Monocyte apoptotic bodies are vehicles for influenza A virus propagation
Georgia K Atkin-Smith, Mubing Duan, Damien J Zanker, Liyen Loh, Thi HO Nguyen, Marios Koutsakos, Tien Nguyen, Xiangrui Jiang, Julio Carrera, Thanh Kha Phan, Chuanxin Liu, Stephanie Paone, Sara Oveissi, Amy L Hodge, Amy A Baxter, Katherine Kedzierska, Jason M Mackenzie, Mark D Hulett, Pamuk Bilsel, Weisan Chen
The disassembly of apoptotic cells into small membrane-bound vesicles termed apoptotic bodies (ApoBDs) is a hallmark of apoptosis;..
Breadth of concomitant immune responses prior to patient recovery: a case report of non-severe COVID-19
Irani Thevarajan, Thi HO Nguyen, Marios Koutsakos, Julian Druce, Leon Caly, Carolien E van de Sandt, Xiaoxiao Jia, Suellen Nicholson, Mike Catton, Benjamin Cowie, Steven YC Tong, Sharon R Lewin, Katherine Kedzierska
Multiplex Screening Assay for Identifying Cytotoxic CD8( ) T Cell Epitopes
Chek Meng Poh, Jian Zheng, Rudragouda Channappanavar, Zi Wei Chang, Thi HO Nguyen, Laurent Renia, Katherine Kedzierska, Stanley Perlman, Leo LM Poon
The cytotoxicity of epitope-specific CD8+ T cells is usually measured indirectly through IFNγ production. Existing assays that dir..
Human Mucosal-Associated Invariant T Cells in Older Individuals Display Expanded TCR alpha beta Clonotypes with Potent Antimicrobial Responses
Liyen Loh, Nicholas A Gherardin, Sneha Sant, Ludivine Grzelak, Jeremy Chase Crawford, Nicola L Bird, Hui-Fern Koay, Carolien E van de Sandt, Marcela L Moreira, Martha Lappas, E Kaitlynn Allen, Jane Crowe, Thomas Loudovaris, Katie L Flanagan, Kylie M Quinn, Jamie Rossjohn, Paul G Thomas, Sidonia BG Eckle, James McCluskey, Dale I Godfrey
Mucosal-associated invariant T (MAIT) cells are important for immune responses against microbial infections. Although known to und..
Influenza A Virus-Infected Lung Epithelial Cell Co-Culture with Human Peripheral Blood Mononuclear Cells
Liyen Loh, Marios Koutsakos, Katherine Kedzierska, Timothy SC Hinks
Sensing of influenza A virus (IAV) infection by pattern recognition receptors can occur by either direct infection of lung epithel..
Challenging immunodominance of influenza-specific CD8( ) T cell responses restricted by the risk-associated HLA-A*68:01 allomorph
CE van de Sandt, EB Clemens, EJ Grant, LC Rowntree, S Sant, H Halim, J Crowe, AC Cheng, TC Kotsimbos, M Richards, A Miller, SYC Tong, J Rossjohn, THO Nguyen, S Gras, W Chen, K Kedzierska
Although influenza viruses lead to severe illness in high-risk populations, host genetic factors associated with severe disease ar..
Characterization of Human Mucosal-associated Invariant T (MAIT) Cells
Michael NT Souter, Liyen Loh, Shihan Li, Bronwyn S Meehan, Nicholas A Gherardin, Dale I Godfrey, Jamie Rossjohn, David P Fairlie, Katherine Kedzierska, Daniel G Pellicci, Zhenjun Chen, Lars Kjer-Nielsen, Alexandra J Corbett, James McCluskey, Sidonia BG Eckle
Mucosal‐associated invariant T (MAIT) cells are a subset of unconventional T cells restricted by the major histocompatibility comp..
A divergent transcriptional landscape underpins the development and functional branching of MAIT cells
H-F Koay, S Su, D Amann-Zalcenstein, SR Daley, I Comerford, L Miosge, CE Whyte, IE Konstantinov, Y d'Udekem, T Baldwin, PF Hickey, SP Berzins, JYW Mak, Y Sontani, CM Roots, T Sidwell, A Kallies, Z Chen, S Nussing, K Kedzierska
MR1-restricted mucosal-associated invariant T (MAIT) cells play a unique role in the immune system. These cells develop intrathymi..
Recalling the Future: Immunological Memory Toward Unpredictable Influenza Viruses
Maria Auladell, Xiaoxiao Jia, Luca Hensen, Brandon Chua, Annette Fox, Thi HO Nguyen, Peter C Doherty, Katherine Kedzierska
Persistent and durable immunological memory forms the basis of any successful vaccination protocol. Generation of pre-existing mem..
TCF-1 limits the formation of Tc17 cells via repression of the MAF-ROR gamma t axis
Lisa A Mielke, Yang Liao, Ella Bridie Clemens, Matthew A Firth, Brigette Duckworth, Qiutong Huang, Francisca F Almeida, Michael Chopin, Hui-Fern Koay, Carolyn A Bell, Soroor Hediyeh-Zadeh, Simone L Park, Dinesh Raghu, Jarny Choi, Tracy L Putoczki, Philip D Hodgkin, Ashley E Franks, Laura K Mackay, Dale Godfrey, Melissa J Davis
Interleukin (IL)-17-producing CD8+ T (Tc17) cells have emerged as key players in host-microbiota interactions, infection, and canc..
Divergent SATB1 expression across human life span and tissue compartments
Simone Nussing, Hui-Fern Koay, Sneha Sant, Thomas Loudovaris, Stuart I Mannering, Martha Lappas, Yves d'Udekem, Igor E Konstantinov, Stuart P Berzins, Guus F Rimmelzwaan, Stephen J Turner, E Bridie Clemens, Dale I Godfrey, HO Nguyen Thi, Katherine Kedzierska
Special AT-rich binding protein-1 (SATB1) is a global chromatin organizer capable of activating or repressing gene transcription i..
Human CD8( ) T cell cross-reactivity across influenza A, B and C viruses
Marios Koutsakos, Patricia T Illing, Thi HO Nguyen, Nicole A Mifsud, Jeremy Chase Crawford, Simone Rizzetto, Auda A Eltahla, E Bridie Clemens, Sneha Sant, Brendon Y Chua, Chinn Yi Wong, E Kaitlynn Allen, Don Teng, Pradyot Dash, David F Boyd, Ludivine Grzelak, Weiguang Zeng, Aeron C Hurt, Ian Barr, Steve Rockman
Influenza A, B and C viruses (IAV, IBV and ICV, respectively) circulate globally and infect humans, with IAV and IBV causing the m..
Multiplex Droplet Digital PCR Assay for Quantification of Human T-Cell Leukemia Virus Type 1 Subtype c DNA Proviral Load and T Cells from Blood and Respiratory Exudates Sampled in a Remote Setting
David Yurick, Georges Khoury, Bridle Clemens, Liyen Loh, Hai Pham, Katherine Kedzierska, Lloyd Einsiedel, Damian Purcell
During human T-cell leukemia virus type 1 (HTLV-1) infection, the frequency of cells harboring an integrated copy of viral cDNA, t..
Distinguishing naive- from memory-derived human B cells during acute responses
Maria Auladell, Ho Nguyen Thi, Beatriz Garcillan, Fabienne Mackay, Katherine Kedzierska, Annette Fox
OBJECTIVES: A fundamental question in influenza research is whether antibody titre decline upon successive exposure to variant str..
Human gamma delta T-cell receptor repertoire is shaped by influenza viruses, age and tissue compartmentalisation
Sneha Sant, Misty R Jenkins, Pradyot Dash, Katherine A Watson, Zhongfang Wang, Angela Pizzolla, Marios Koutsakos, Thi HO Nguyen, Martha Lappas, Jane Crowe, Tom Loudovaris, Stuart Mannering, Glen P Westall, Tom C Kotsimbos, Allen C Cheng, Linda Wakim, Peter C Doherty, Paul G Thomas, Liyen Loh, Katherine Kedzierska
BACKGROUND: Although γδ T cells comprise up to 10% of human peripheral blood T cells, questions remain regarding their role in dis..
The Drivers of Pathology in Zoonotic Avian influenza: The interplay Between Host and Pathogen
William SJ Horman, Thi HO Nguyen, Katherine Kedzierska, Andrew GD Bean, Daniel S Layton
The emergence of zoonotic strains of avian influenza (AI) that cause high rates of mortality in people has caused significant glob..
Age-Related Decline in Primary CD8( ) T Cell Responses Is Associated with the Development of Senescence in Virtual Memory CD8( ) T Cells
Kylie M Quinn, Annette Fox, Kim L Harland, Brendan E Russ, Jasmine Li, Thi HO Nguyen, Liyen Loh, Moshe Olshanksy, Haroon Naeem, Kirill Tsyganov, Florian Wiede, Rosela Webster, Chantelle Blyth, Xavier YX Sng, Tony Tiganis, David Powell, Peter C Doherty, Stephen J Turner, Katherine Kedzierska, Nicole L La Gruta
Age-associated decreases in primary CD8+ T cell responses occur, in part, due to direct effects on naive CD8+ T cells to reduce in..
Enumeration, functional responses and cytotoxic capacity of MAIT cells in newly diagnosed and relapsed multiple myeloma
Nicholas A Gherardin, Liyen Loh, Lorenztino Admojo, Alexander J Davenport, Kelden Richardson, Amy Rogers, Phillip K Darcy, Misty R Jenkins, H Miles Prince, Simon J Harrison, Hang Quach, David P Fairlie, Katherine Kedzierska, James McCluskey, Adam P Uldrich, Paul J Neeson, David S Ritchie, Dale I Godfrey
Mucosal-associated invariant T (MAIT) cells are T cells that recognise vitamin-B derivative Ag presented by the MHC-related-protei..
Maintenance of the EBV-specific CD8 TCR alpha beta repertoire in immunosuppressed lung transplant recipients
Ho Nguyen Thi, Nicola L Bird, Emma J Grant, John J Miles, Paul G Thomas, Tom C Kotsimbos, Nicole A Mifsud, Katherine Kedzierska
Epstein-Barr virus (EBV) is one of the most common viruses in humans, capable of causing life-threatening infections and cancers i..
Human mucosal-associated invariant T cells contribute to antiviral influenza immunity via IL-18-dependent activation
Liyen Loh, Zhongfang Wang, Sneha Sant, Marios Koutsakos, Sinthujan Jegaskanda, Alexandra J Corbett, Ligong Liu, David P Fairlie, Jane Crowe, Jamie Rossjohn, Jianqing Xu, Peter C Doherty, James McCluskey, Katherine Kedzierska
Mucosal-associated invariant T (MAIT) cells are innate-like T lymphocytes known to elicit potent immunity to a broad range of bact..
Linking the T cell receptor to the single cell transcriptome in antigen-specific human T cells
Auda A Eltahla, Simone Rizzetto, Mehdi R Pirozyan, Brigid D Betz-Stablein, Vanessa Venturi, Katherine Kedzierska, Andrew R Lloyd, Rowena A Bull, Fabio Luciani
Heterogeneity of T cells is a hallmark of a successful adaptive immune response, harnessing the vast diversity of antigen-specific..