LIMITING THE IMPACT OF INFLUENZA
Grant number: 1071916 | Funding period: 2015 - 2019
The development of better ways to prevent and treat influenza infection will be a major step forward in lessening the impact of the virus in communities worldwide. We have assembled a research team of seven groups who will determine the ways in which the effects of influenza can be mitigated through an understanding of the factors which lead to severe disease, and how these can be lessened by novel vaccination and treatment strategies.
Related publications (74)
Gene Segment Interactions Can Drive the Emergence of Dominant Yet Suboptimal Gene Constellations During Influenza Virus Reassortment
Sanja Trifkovic, Brad Gilbertson, Emily Fairmaid, Joanna Cobbin, Steven Rockman, Lorena EE Brown
A segmented genome enables influenza virus to undergo reassortment when two viruses infect the same cell. Although reassortment is..
CD8( ) T cell landscape in Indigenous and non-Indigenous people restricted by influenza mortality-associated HLA-A*24:02 allomorph
Luca Hensen, Patricia T Illing, E Bridie Clemens, Thi HO Nguyen, Marios Koutsakos, Carolien E van de Sandt, Nicole A Mifsud, Andrea T Nguyen, Christopher Szeto, Brendon Y Chua, Hanim Halim, Simone Rizzetto, Fabio Luciani, Liyen Loh, Emma J Grant, Phillipa M Saunders, Andrew G Brooks, Steve Rockman, Tom C Kotsimbos, Allen C Cheng
Indigenous people worldwide are at high risk of developing severe influenza disease. HLA-A*24:02 allele, highly prevalent in Indig..
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..
Influenza A virus infection-induced macroautophagy facilitates MHC class II-restricted endogenous presentation of an immunodominant viral epitope.
Jieru Deng, Chunni Lu, Chuanxin Liu, Sara Oveissi, W Douglas Fairlie, Erinna F Lee, Pamuk Bilsel, Hamsa Puthalakath, Weisan Chen
CD4+ T cells recognize peptides presented by major histocompatibility complex class II molecules (MHC-II). These peptides are gene..
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-..
Integrated immune dynamics define correlates of COVID-19 severity and antibody responses
Marios Koutsakos, Louise C Rowntree, Luca Hensen, Brendon Y Chua, Carolien E van de Sandt, Jennifer R Habel, Wuji Zhang, Xiaoxiao Jia, Lukasz Kedzierski, Thomas M Ashhurst, Givanna H Putri, Felix Marsh-Wakefield, Mark N Read, Davis N Edwards, E Bridie Clemens, Chinn Yi Wong, Francesca L Mordant, Jennifer A Juno, Fatima Amanat, Jennifer Audsley
SARS-CoV-2 causes a spectrum of COVID-19 disease, the immunological basis of which remains ill defined. We analyzed 85 SARS-CoV-2-..
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..
High expression of CD38 and MHC class II on CD8 T cells during severe influenza disease reflects bystander activation and trogocytosis
Xiaoxiao Jia, Brendon Chua, Liyen Loh, Marios Koutsakos, Lukasz Kedzierski, Moshe Olshanski, William Heath, Jianqing Xu, Zhongfang Wang, Katherine Kedzierska
Although co-expression of CD38 and HLA-DR on CD8 + T cells reflects activation during influenza, SARS-CoV-2, Dengue, Ebola and HIV..
High expression of CD38 and MHC class II on CD8 T cells during severe influenza disease reflects bystander activation and trogocytosis.
Xiaoxiao Jia, Brendon Y Chua, Liyen Loh, Marios Koutsakos, Lukasz Kedzierski, Moshe Olshansky, William R Heath, So Young Chang, Jianqing Xu, Zhongfang Wang, Katherine Kedzierska
Objectives: Although co-expression of CD38 and HLA-DR reflects T-cell activation during viral infections, high and prolonged CD38+..
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..
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..
HLA-B*27:05 alters immunodominance hierarchy of universal influenza-specific CD8( )T cells
Sneha Sant, Sergio M Quinones-Parra, Marios Koutsakos, Emma J Grant, Thomas Loudovaris, Stuart I Mannering, Jane Crowe, Carolien E van de Sandt, Guus F Rimmelzwaan, Jamie Rossjohn, Stephanie Gras, Liyen Loh, Thi HO Nguyen, Katherine Kedzierska
Seasonal influenza virus infections cause 290,000-650,000 deaths annually and severe morbidity in 3-5 million people. CD8+ T-cell ..
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..
Distinct systems serology features in children, elderly and COVID patients
Kevin Selva, Carolien van de Sandt, Melissa Lemke, Christina Lee, Suzanne Shoffner, Brendon Chua, Thi HO Nguyen, Louise Rowntree, Luca Hensen, Marios Koutsakos, Chinn Yi Wong, David Jackson, Katie Flanagan, Jane Crowe, Allen Cheng, Denise Doolan, Fatima Amanat, Florian Krammer, Keith Chappell, Naphak Modhiran
SARS-CoV-2, the pandemic coronavirus that causes COVID-19, has infected millions worldwide, causing unparalleled social and econom..
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;..
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..
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..
The structure of the influenza A virus genome
Bernadeta Dadonaite, Brad Gilbertson, Michael L Knight, Sanja Trifkovic, Steven Rockman, Alain Laederach, Lorena E Brown, Ervin Fodor, David LV Bauer
Influenza A viruses (IAVs) constitute a major threat to human health. The IAV genome consists of eight single-stranded viral RNA s..
Activation and In Vivo Evolution of the MAIT Cell Transcriptome in Mice and Humans Reveals Tissue Repair Functionality
Timothy SC Hinks, Emanuele Marchi, Maisha Jabeen, Moshe Olshansky, Ayako Kurioka, Troi J Pediongco, Bronwyn S Meehan, Lyudmila Kostenko, Stephen J Turner, Alexandra J Corbett, Zhenjun Chen, Paul Klenerman, James McCluskey
Mucosal-associated invariant T (MAIT) cells are MR1-restricted innate-like T cells conserved across mammalian species, including m..
Microbiota-Derived Short-Chain Fatty Acids Promote the Memory Potential of Antigen-Activated CD8( ) T Cells
Annabel Bachem, Christina Makhlouf, Katrina J Binger, David P de Souza, Deidra Tull, Katharina Hochheiser, Paul G Whitney, Daniel Fernandez-Ruiz, Sabrina Dahling, Wolfgang Kastemuller, Johanna Jonsson, Elise Gressier, Andrew M Lew, Carolina Perdomo, Andreas Kupz, William Figgett, Fabienne Mackay, Moshe Oleshansky, Brendan E Russ, Ian A Parish
Interactions with the microbiota influence many aspects of immunity, including immune cell development, differentiation, and funct..
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..
Quantification of epitope abundance reveals the effect of direct and cross-presentation on influenza CTL responses
Ting Wu, Jing Guan, Andreas Handel, David C Tscharke, John Sidney, Alessandro Sette, Linda M Wakim, Xavier YX Sng, Paul G Thomas, Nathan P Croft, Anthony W Purcell, Nicole L La Gruta
The magnitude of T cell responses to infection is a function of the naïve T cell repertoire combined with the context and duration..
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..
CD4( ) T help promotes influenza virus-specific CD8( ) T cell memory by limiting metabolic dysfunction
Jolie G Cullen, Hayley A McQuilten, Kylie M Quinn, Moshe Olshansky, Brendan E Russ, Alison Morey, Sanna Wei, Julia E Prier, Nicole L La Gruta, Peter C Doherty, Stephen J Turner
There is continued interest in developing novel vaccine strategies that induce establish optimal CD8+ cytotoxic T lymphocyte (CTL)..
Unique Transcriptional Architecture in Airway Epithelial Cells and Macrophages Shapes Distinct Responses following Influenza Virus Infection Ex Vivo
Joel Z Ma, Wy Ching Ng, Luke Zappia, Linden J Gearing, Moshe Olshansky, Kym Pham, Karey Cheong, Arthur Hsu, Stephen J Turner, Odilia Wijburg, Sarah L Londrigan, Andrew G Brooks, Patrick C Reading
Airway epithelial cells and macrophages differ markedly in their responses to influenza A virus (IAV) infection. To investigate tr..
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..
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..
Activation and in vivo evolution of the MAIT cell transcriptome in mice and humans reveals diverse functionality
Timothy SC Hinks, Emanuele Marchi, Maisha Jabeen, Moshe Olshansky, Ayako Kurioka, Troi Pediongco, Bronwyn Meehan, Lyudmila Kostenko, Stephen Turner, Alexandra Corbett, Zhenjun Chen, Paul Klenerman, James McCluskey
Mucosal-associated invariant T (MAIT) cells are MR1-restricted innate-like T cells conserved across mammalian species, including m..
Limited Phenotypic and Functional Plasticity of Influenza Virus-Specific Memory CD8( ) T Cells during Activation in an Alternative Cytokine Environment
Kim L Harland, Annette Fox, Simone Nussing, Luca Hensen, Katherine Kedzierska, Stephen J Turner, Anne Kelso
Naive CD8+ T cells show phenotypic, functional, and epigenetic plasticity, enabling differentiation into distinct cellular states...
Single-Cell Approach to Influenza Specific CD8( ) T Cell Receptor Repertoires Across Different Age Groups, Tissues, and Following Influenza Virus Infection
Sneha Sant, Ludiyine Grzelak, Zhongfang Wang, Angela Pizzollal, Manbs Koutsakos, Jane Crowe, Thomas Loudoyaris, Stuart I Mannering, Glen P Westall, Linda M Wakiml, Jamie Rossjohn, Stephanie Gras, Michael Richards, Jianqing Xu, Paul G Thomas, Liyen Loh, Thi H Nguyen, Katherine Kedzierska
CD8+ T cells recognizing antigenic peptides derived from conserved internal viral proteins confer broad protection against distinc..
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..
Exposure of Human CD8( ) T Cells to Type-2 Cytokines Impairs Division and Differentiation and Induces Limited Polarization
Annette Fox, Kim L Harland, Katherine Kedzierska, Anne Kelso
Effector CD8+ T cells generally produce type-1 cytokines and mediators of the perforin/granzyme cytolytic pathway, yet type-2-pola..
MAIT cells contribute to protection against lethal influenza infection in vivo
Bonnie van Wilgenburg, Liyen Loh, Zhenjun Chen, Troi Pediongco, Huimeng Wang, Mai Shi, Zhe Zhao, Marios Koutsakos, Simone Nüssing, Sneha Sant, Zhongfang Wang, Criselle D’Souza, Catarina Almeida, Lyudmila Kostenko, Sidonia BG Eckle, Bronwyn Meehan, Dale Godfrey, Patrick Reading, Alexandra Corbett, James McCluskey
Mucosal associated invariant T (MAIT) cells are evolutionarily-conserved, innate-like lymphocytes which are abundant in human lung..
Clonally diverse CD38( )HLA-DR( )CD8( ) T cells persist during fatal H7N9 disease
Zhongfang Wang, Lingyan Zhu, Thi HO Nguyen, Yanmin Wan, Sneha Sant, Sergio M Quinones-Parra, Jeremy Chase Crawford, Auda A Eltahla, Simone Rizzetto, Rowena A Bull, Chenli Qiu, Marios Koutsakos, E Bridie Clemens, Liyen Loh, Tianyue Chen, Lu Liu, Pengxing Cao, Yanqin Ren, Lukasz Kedzierski, Tom Kotsimbos
Severe influenza A virus (IAV) infection is associated with immune dysfunction. Here, we show circulating CD8+ T-cell profiles fro..
Circulating T-FH cells, serological memory, and tissue compartmentalization shape human influenza-specific B cell immunity
Marios Koutsakos, Adam K Wheatley, Liyen Loh, E Bridie Clemens, Sneha Sant, Simone Nussing, Annette Fox, Amy W Chung, Karen L Laurie, Aeron C Hurt, Steve Rockman, Martha Lappas, Thomas Loudovaris, Stuart I Mannering, Glen P Westall, Michael Elliot, Stuart G Tangye, Linda M Wakim, Stephen J Kent, Thi HO Nguyen
Immunization with the inactivated influenza vaccine (IIV) remains the most effective strategy to combat seasonal influenza infecti..
Influenza-specific lung-resident memory T cells are proliferative and polyfunctional and maintain diverse TCR profiles
Angela Pizzolla, Thi HO Nguyen, Sneha Sant, Jade Jaffar, Tom Loudovaris, Stuart I Mannering, Paul G Thomas, Glen P Westall, Katherine Kedzierska, Linda M Wakim
The human lung harbors a large population of resident memory T cells (Trm cells). These cells are perfectly positioned to mediate ..
Perturbed CD8( ) T cell immunity across universal influenza epitopes in the elderly
Thi HO Nguyen, Sneha Sant, Nicola L Bird, Emma J Grant, E Bridie Clemens, Marios Koutsakos, Sophie A Valkenburg, Stephanie Gras, Martha Lappas, Anthony Jaworowski, Jane Crowe, Liyen Loh, Katherine Kedzierska
Influenza epidemics lead to severe illness, life-threatening complications, and deaths, especially in the elderly. As CD8+ T cells..
Augmenting Influenza-Specific T Cell Memory Generation with a Natural Killer T Cell-Dependent Glycolipid-Peptide Vaccine
Regan J Anderson, Jasmine Li, Lukasz Kedzierski, Benjamin J Compton, Colin M Hayman, Taryn L Osmond, Ching-wen Tang, Kathryn J Farrand, Hui-Fern Koay, Catarina Filipa Dos Santos Sa E Almeida, Lauren R Holz, Geoffrey M Williams, Margaret A Brimble, Zhongfang Wang, Marios Koutsakos, Katherine Kedzierska, Dale I Godfrey, Ian F Hermans, Stephen J Turner, Gavin F Painter
The development of a universal vaccine for influenza A virus (IAV) that does not require seasonal modification is a long-standing ..
Structure-function relationships of protein-lipopeptide complexes and influence on immunogenicity
Acep R Wijayadikusumah, Lucy C Sullivan, David C Jackson, Brendon Y Chua
The lipopeptide, R4Pam2Cys, associates electrostatically with soluble protein antigens and significantly enhances their ability to..
Extrinsically derived TNF is primarily responsible for limiting antiviral CD8 T cell response magnitude
Kylie M Quinn, Wan-Ting Kan, Katherine A Watson, Brian J Liddicoat, Natasha G Swan, Hayley McQuilten, Alice E Denton, Jasmine Li, Weisan Chen, Lorena E Brown, David C Jackson, Patrick C Reading, Peter C Doherty, Katherine Kedzierska, Lukasz Kedzierski, Stephen J Turner, Nicole L La Gruta
TNF is a pro-inflammatory cytokine produced by both lymphoid and non-lymphoid cells. As a consequence of the widespread expression..
Rapid evolution of the PB1-F2 virulence protein expressed by human seasonal H3N2 influenza viruses reduces inflammatory responses to infection
Julie McAuley, Yi-Mo Deng, Brad Gilbertson, Charley Mackenzie-Kludas, Ian Barr, Lorena Brown
Influenza A virus (IAV) PB1-F2 protein has been linked to viral virulence. Strains of the H3N2 subtype historically express full-l..
PEGylation of a TLR2-agonist-based vaccine delivery system improves antigen trafficking and the magnitude of ensuing antibody and CD8( ) T cell responses
Toshiki Sekiya, Junya Yamagishi, John Henry V Gray, Paul G Whitney, Axel Martinelli, Weiguang Zeng, Chinn Yi Wong, Chihiro Sugimoto, David C Jackson, Brendon Y Chua
The lipopeptide R4Pam2Cys is an agonist for toll-like receptor-2 (TLR2), a key pathogen-associated molecular pattern receptor expr..
Fc functional antibodies in humans with severe H7N9 and seasonal influenza
Hillary A Vanderven, Lu Liu, Fernanda Ana-Sosa-Batiz, Thi HO Nguyen, Yanmin Wan, Bruce Wines, P Mark Hogarth, Danielle Tilmanis, Arnold Reynaldi, Matthew S Parsons, Aeron C Hurt, Miles P Davenport, Tom Kotsimbos, Allen C Cheng, Katherine Kedzierska, Xiaoyan Zhang, Jianqing Xu, Stephen J Kent
BACKGROUND: Both seasonal and novel avian influenza viruses can result in severe infections requiring hospitalization. Anti-influe..
Quantifiable predictive features define epitope-specific T cell receptor repertoires
Pradyot Dash, Andrew J Fiore-Gartland, Tomer Hertz, George C Wang, Shalini Sharma, Aisha Souquette, Jeremy Chase Crawford, E Bridie Clemens, Thi HO Nguyen, Katherine Kedzierska, Nicole L La Gruta, Philip Bradley, Paul G Thomas
T cells are defined by a heterodimeric surface receptor, the T cell receptor (TCR), that mediates recognition of pathogen-associat..
Dominant protection from HLA-linked autoimmunity by antigen-specific regulatory T cells
Joshua D Ooi, Jan Petersen, Yu H Tan, Megan Huynh, Zoe J Willett, Sri H Ramarathinam, Peter J Eggenhuizen, Khai L Loh, Katherine A Watson, Poh Y Gan, Maliha AA Likhan, Nadine L Dudek, Andreas Handel, Billy G Hudson, Lars Fugger, David A Power, Stephen G Holt, P Toby Coates, Jon W Gregersen, Anthony W Purcell
Susceptibility and protection against human autoimmune diseases, including type I diabetes, multiple sclerosis, and Goodpasture di..
Understanding CD8( ) T-cell responses toward the native and alternate HLA-A*02:01-restricted WT1 epitope
Thi HO Nguyen, Amabel CL Tan, Sue D Xiang, Anne Goubier, Kim L Harland, E Bridie Clemens, Magdalena Plebanski, Katherine Kedzierska
The Wilms' tumor 1 (WT1) antigen is expressed in solid and hematological malignancies, but not healthy tissues, making it a promis..
Modelling cross-reactivity and memory in the cellular adaptive immune response to influenza infection in the host
Ada WC Yan, Pengxing Cao, Jane M Heffernan, Jodie McVernon, Kylie M Quinn, Nicole L La Gruta, Karen L Laurie, James M McCaw
The cellular adaptive immune response plays a key role in resolving influenza infection. Experiments where individuals are success..
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..
Establishment of memory CD8( ) T cells with live attenuated influenza virus across different vaccination doses
Zhongfang Wang, Lukasz Kedzierski, Simone Nuessing, Brendon Yew Loong Chua, Sergio M Quiones-Parra, Victor C Huber, David C Jackson, Paul G Thomas, Katherine Kedzierska
FluMist has been used in children and adults for more than 10 years. As pre-existing CD8+ T cell memory pools can provide heterolo..
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..
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..
Ubiquitin ligase MARCH 8 cooperates with CD83 to control surface MHC II expression in thymic epithelium and CD4 T cell selection
Haiyin Liu, Reema Jain, Jing Guan, Vivian Vuong, Satoshi Ishido, Nicole L La Gruta, Daniel H Gray, Jose A Villadangos, Justine D Mintern
Major histocompatibility complex class II (MHC II) expression is tightly regulated, being subjected to cell type-specific mechanis..
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..
Influenza NA and PB1 Gene Segments Interact during the Formation of Viral Progeny: Localization of the Binding Region within the PB1 Gene
Brad Gilbertson, Tian Zheng, Marie Gerber, Anne Printz-Schweigert, Chi Ong, Roland Marquet, Catherine Isel, Steven Rockman, Lorena Brown
The influenza A virus genome comprises eight negative-sense viral RNAs (vRNAs) that form individual ribonucleoprotein (RNP) comple..
Induction of memory cytotoxic T cells to influenza A virus and subsequent viral clearance is not modulated by PB1-F2-dependent inflammasome activation
Patricia Hoi Yee Lee, Nicola Bird, Charley MacKenzie-Kludas, Ashley Mansell, Katherine Kedzierska, Lorena Brown, Julie McAuley
Expression of the viral virulence protein PB1-F2 during infection has been linked to NLRP3 inflammasome complex activation in macr..
Molecular basis for universal HLA-A(star)0201-restricted CD8( ) T-cell immunity against influenza viruses
Sophie A Valkenburg, Tracy M Josephs, E Bridie Clemens, Emma J Grant, Thi HO Nguyen, George C Wang, David A Price, Adrian Miller, Steven YC Tong, Paul G Thomas, Peter C Doherty, Jamie Rossjohn, Stephanie Gras, Katherine Kedzierska
Memory CD8(+)T lymphocytes (CTLs) specific for antigenic peptides derived from internal viral proteins confer broad protection aga..
Towards identification of immune and genetic correlates of severe influenza disease in Indigenous Australians
E Bridie Clemens, Emma J Grant, Zhongfang Wang, Stephanie Gras, Peta Tipping, Jamie Rossjohn, Adrian Miller, Steven YC Tong, Katherine Kedzierska
Indigenous populations, including Indigenous Australians, are highly susceptible to severe influenza disease and the underlying me..
CD11b immunophenotyping identifies inflammatory profiles in the mouse and human lungs
M Duan, DP Steinfort, D Smallwood, M Hew, W Chen, M Ernst, LB Irving, GP Anderson, ML Hibbs
The development of easily accessible tools for human immunophenotyping to classify patients into discrete disease endotypes is adv..
Heightened self-reactivity associated with selective survival, but not expansion, of naive virus-specific CD8( ) T cells in aged mice
Kylie M Quinn, Sophie G Zaloumis, Tania Cukalac, Wan-Ting Kan, Xavier YX Sng, Michiko Mirams, Katherine A Watson, James M McCaw, Peter C Doherty, Paul G Thomas, Andreas Handel, Nicole L La Gruta
In advanced age, decreased CD8(+) cytotoxic T-lymphocyte (CTL) responses to novel pathogens and cancer is paralleled by a decline ..
Reducing the impact of influenza-associated secondary pneumococcal infections
Edin J Mifsud, Amabel C Tan, Kirsty R Short, Lorena E Brown, Brendon Y Chua, David C Jackson
When administered prophylactically, we show that the Toll-like receptor-2 (TLR-2) agonist PEG-Pam2Cys (pegylated-S-(2,3-bis(palmit..
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..
Generation of adaptive immune responses following influenza virus challenge is not compromised by pre-treatment with the TLR-2 agonist Pam(2)Cys
Edin Jessica Mifsud, Amabel CL Tan, Lorena Elizabeth Brown, Brendon Yew Loong Chua, David C Jackson
Immunostimulatory agents provide a new category of anti-microbial agents that activate the host's innate immune system allowing co..