Applied, cellular and molecular immunology, medical microbiology, vaccine immunology and technology
Tuberculosis (TB) caused by Mycobacterium tuberculosis is a deadly lung disease killing more people every year than any other bacterial infection. One third of the world's population is estimated to be infected, and New Zealand is not exempt. We believe the best way to control the global TB epidemic is through vaccination. Our lab's research is focused on understanding the generation and maintenance of immunological memory in order to improve vaccination against TB.
The only available vaccine against TB is bacille Calmette Guérin (BCG). The BCG vaccine does not reliably protect against adult TB lung disease, the most common form of TB. Our struggle to develop a more effective vaccine stems, in part, from a lack of understanding of the protective memory immune response against TB. In our lab we are reevaluating the contribution of T cells to protective immunological memory against TB, as well as investigating the role of a recently discovered subset of immune cells known as Innate Lymphoid Cells (ILCs) in the recall response to TB. Ultimately, we will use this knowledge to inform the design of a new, improved TB vaccine.
Collaborators: James Ussher, Ayesha Verrall and Philip Hill (University of Otago)
Funding: University of Otago Research Grant
There are many different subsets of DCs that can be distinguished by phenotype and function;the role that each of the different DC subsets play during early TB infection is unclear. In this project we are assessing the ability of the different DC subsets to control early infection and to activate the adaptive immune response (Project 2a). We are also investigating novel antibacterial agents, and their ability to control mycobacterial growth or kill mycobacteria inside phagocytes (Project 2b).
Collaborators: Siouxsie Wiles (University of Auckland)
Funding: University of Otago Research Grant
One way to improve the TB vaccine is through the use of novel vaccine formulations, designed to protect the immune-stimulating protein (antigen) from destruction or to enable its persistence in the body. If more antigen reaches the appropriate immune cells, this may lead to a stronger immune response; and if antigen is able to persist in the body this may reduce the number of booster shots required, which would improve immunisation completion rates.
Collaborators: Sarah Hook (University of Otago), Thomas Proft (University of Auckland), Bernd Rehm (Massey University)
Funding: Marsden Fund
Design of Bacterial Inclusion Bodies as Antigen Carrier Systems. Chen S, Sandford S, Joanna Kirman J, Rehm BHA Advanced Biosystems 2018 v2 (11) article 1800118
Langerin+ CD8α+ Dendritic Cells Drive Early CD8+ T Cell Activation and IL-12 Production During Systemic Bacterial Infection. Prendergast KA, Daniels NJ, Petersen TR, Hermans IF, Kirman JR.
Front Immunol. 2018 May 7;9:953.
BCG vaccination drives accumulation and effector function of innate lymphoid cells in murine lungs. Steigler P, Daniels NJ, McCulloch TR, Ryder BM, Sandford SK, Kirman JR. Immunol Cell Biol (2018) 96(4):379-389
The Memory Immune Response to Tuberculosis. Kirman JR, Henao-Tamayo MI, Agger EM. Microbiol Spectr. (2016) Dec;4(6).
IL-1βR-dependent priming of antitumor CD4+ T cells and sustained antitumor immunity after peri-tumoral treatment with MSU and mycobacteria. Kuhn, S., Yang, J., Hyde, E. J., Harper, J. L., Kirman, J. R., & Ronchese, F. (2015). OncoImmunology, 4(10), e1042199.
Sustained in vivo depletion of splenic langerin+ CD8alpha+ dendritic cells is well-tolerated by lang-DTREGFP mice Prendergast KA, Osmond, TL, Ochiai S, Hermans IF, Kirman JR J Immunological Methods (2014) 406:104-9
Increased numbers of monocyte-derived dendritic cells during successful tumor immunotherapy with immune-activiting agents Kuhn S, Hyde EJ, Yang J, Rich FJ, Harper JL, Kirman JR, Ronchese F J Immunol (2013) 191: 1984-92
Detection of inhibitors of phenotypically drug-tolerant Mycobacterium tuberculosis using an in vitro bactericidal screen Bassett IM, Lun S, Bishai WR, Guo H, Kirman JR, Altaf M, O'Toole RF J Microbiol (2013) 51: 651-8
Dendritic cell subsets in mycobacterial infection: control of bacterial growth and T cell responses Prendergast KA, Kirman JR Tuberculosis (2013) 93: 115-122
Oral Vaccination with Lipid-formulated BCG induces a long-lived multifunctional CD4+ T cell memory immune response Ancelet LR, Aldwell FE, Rich FJ, Kirman JR PLoS ONE (2012) 7(9): e45888.
Dissecting memory T cell responses to TB: Concerns using adoptive transfer into immunodeficient mice. Ancelet L, Rich FJ, Delahunt B, Kirman JR Tuberculosis (2012) 92: 422-433
Induction of T cell responses and recruitment of an inflammatory dendritic cell subsets following tumor immunotherapy with Mycobacterium smegmatis Rich FJ, Kuhn S, Hyde EJ, Harper JL, Ronchese F, Kirman JR Cancer Immunol Immunther (2012) 61: 2333-42
Shaping the CD4+ memory immune response against Tuberculosis: the role of antigen persistence, location and multi-functionality. Ancelet L and Kirman JR Biomolecular Concepts 3 (2012) 13-20
A key role for lung-resident memory Lymphocytes in protective immune responses after BCG vaccination Connor LM, Harvie MC, Rich FJ, Quinn KM, Brinkmann V, Le Gros G and Kirman JR European Journal of Immunology 40 (2010) 2482-2492
Geographical differences in the proportion of human group A rotavirus strains within New Zealand during one epidemic season Chandrahasen C, Grimwood K, Redshaw N, Rich FJ, Wood C, Standley J, Kirman JR and the New Zealand Rotavirus Study Group J Med Virol 82 (2010) 897-902
** We are currently seeking a highly motivated, excellent PhD candidate with an excellent academic record **
Laura Hughes BBiomedSc Honours 2018 and Shannon Frewen BSc Honours 2018
Claudia Lewis BBiomedSc Honours 2017 and Lucy Huang BSc Honours 2017
Sarah Sandford BBioMedSc Honours 2016 - David T Jones Prize (top ranked BBioMedSci(Hons) student)
Brin Ryder BSc Honours 2015 - John Miles Prize (top ranked BSc(Hons) student), best 4th year student presentation
Kate Manners BBioMedSc Honours 2014
Stephen Hall BBioMedSc Honours 2013
Mitchell Foster 2018
Charlotte Cairns 2016
Claudia Lewis 2016
Sarah Sandford 2015
Brin Ryder 2014
Joanne Lee 2013
Dayle Keown 2012 - best summer studentship report award
Clare Burn 2012-2014 (Fulbright Science and Innovation Graduate Award recipient 2014)
Dr Kylie Quinn (currently Research Fellow at Monash University, Melbourne, Australia)
Dr Lisa Connor (currently Lecturer at Victoria University of Wellington, NZ)
Dr Lindsay Ancelet (currently Therapeutic Group Manager, PHARMAC, NZ)
Dr Kelly Prendergast (currently Project Officer, Garvan Institute of Medical Research, Sydney, Australia)
Dr Pia Steigler (currently Postdoctoral Fellow at the University of Capetown, South Africa)