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. Our lab is also interested in other respiratory pathogens, such as respiratory syncytial virus (RSV), which causes bronchiolitis in infants.
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 (Project 1a), 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 (Project 1b). Ultimately, we will use this knowledge to inform the design of a new, improved TB vaccine.
Collaborators: Bryce Buddle (AgResearch Hopkirk, Palmerston North), James Ussher (University of Otago), Philip Hill (University of Otago)
Funding: Otago Medical Research Foundation (Project 1a), Dean's Bequest Fund (Project 1b)
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), Khaled Greish (University of Otago)
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: Frank Aldwell (Immune Solutions Ltd), Sarah Hook (University of Otago)
Funding: Sherriff Trust
Respiratory Syncytial Virus (RSV) causes bronchiolitis, an often serious lung infection affecting children <2 years. Bronchiolitis is a leading causes of infant hospitalisation. We are conducting an observational study to determine the typical course of infection in hospitalized New Zealand children, in order to facilitate the implementation of new treatments for RSV disease.
Collaborators: Tristram Ingham and Bernadette Jones (University of Otago, Wellington)
Funding: Janssen Pharmaceuticals
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. doi: 10.1080/2162402X.2015.1042199
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 **
Brin Ryder BSc Honours 2015 - John Miles Prize (top ranked BSc(Hons) student), best 4th year student presentation
Kate Manners BBioMedSci Honours 2014
Stephen Hall BBioMedSci Honours 2013
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 at Monash, Australia: 1st postdoc at National Institutes of Health, USA, 2nd postdoc University of Melbourne, Australia)
Dr Lisa Connor (1st postdoc at Trudeau Institute, USA, 2nd postdoc at Malaghan Institute of Medical Research, NZ)
Dr Lindsay Ancelet (currently postdoctoral fellow at the Malaghan Institute of Medical Research, NZ)
Dr Kelly Prendergast (currently postdoctoral fellow at the University of Sydney, Australia)