Applied, cellular and molecular immunology, medical microbiology, vaccine immunology and technology
Tuberculosis (TB) is a deadly lung disease caused by Mycobacterium tuberculosis (Mtb) that kills 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.
Kirman Lab 2020
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| Kathy Sircombe - Assistant Research Fellow | Dr Naomi Daniels - Postdoctoral Fellow |
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Postgraduate Writing Scholar |
Mitchell Foster - PhD Student | ||
| Reshvinder Kaur Bedi - PGDip BMLSc | Natasha Nair BSc (Hons) |
Not all Mtb strains are equal. Beijing genotype Mtb strains display selective advantages over other genotypes including: greater virulence in animal studies; a higher capacity to withstand tuberculosis treatment; and increased relapse after treatment. The existing TB vaccine, bacillus Calmette–Guérin (BCG), is protective in ~50% of cases when delivered intradermally; however, BCG does not protect equally against all Mtb strains. In a case contact study of over 400 TB case households and over 1400 contacts in Indonesia (in which 1/3 of isolates were Beijing genotype), we found that although BCG vaccination was associated with protection in contacts exposed to non-Beijing strains there was no evidence of BCG protection against IGRA conversion in contacts exposed to a Beijing strain. In this project, we test the hypothesis that the Beijing TB strain evades and subverts BCG-mediated trained innate immunity using a mouse model of BCG vaccination and TB challenge.
Collaborators: Marcela Henao-Tamayo (Colorado State University), Philip Hill (University of Otago)
Funding: Marsden Fund of New Zealand
There are many different subsets of macrophages and DCs that can be distinguished by phenotype and function; the role that each subset plays during early TB infection is unclear. In this project we are assessing the ability of the different DC subsets to control early infection, using molecular and cellular methods (RNA-Seq, qRT-CPR, flow cytometry).
Collaborators: Marcela Henao-Tamayo (Colorado State University), Siouxsie Wiles (University of Auckland)
Funding: Otago Medical Research Foundation (grant completed)
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: Thomas Proft (University of Auckland)
Funding: Marsden Fund (grant completed)
The BCG vaccination can train innate immune cells to exhibit features of immunological memory, without the specificity of the adaptive immune response. In this study, we investigate the ability of the BCG vaccine to protect against polymicrobial skin abscess formation.
Collaborators: Daniel Pletzer (University of Otago)
Funding: BMS-Dean's Bequest
Gr1int/high Cells Dominate the Early Phagocyte Response to Mycobacterial Lung Infection in Mice Brin M. Ryder1, Sarah K. Sandford1, Kate M. Manners1, James P. Dalton2, Siouxsie Wiles and Joanna R. Kirman Frontiers in Microbiology 2019 March 8
Design of Bacterial Inclusion Bodies as Antigen Carrier Systems. Chen S, Sandford S, 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 *
Radio New Zealand 2020 Our immune system vs coronavirus: ‘I think of it as an orchestra' (28 mins, produced by Allison Balance)
Stuff Podcast 2020 Claiming immunity: should COVID-19 survivors get better treatment? (26 mins, produced by Adam Dudding and Eugene Bingham)
ABC Radio National (Australia) How long will a COVID-19 vaccine take (42 mins, presented by Rod Quinn)
Otago Daily Times Therapeutic Drugs Needed (2020)
South China Morning Post Coronavirus vaccine will not be a magic bullet, scientists warn (by Simone McCarthy, 2020)
The Conversation, Stuff Could BCG, a 100-year-old vaccine for tuberculosis, protect against Covid-19? by Kylie Quinn, Jo Kirman, Katie Louise Flanagan and Magdalena Plebanski
Ten common misconceptions about the COVID-19 vaccine, debunked (by Emily Writes, 2021)
Radio New Zealand 2021 COVID vaccine could soon be approved (9 minutes, produced by the The Panel)
Newstalk ZB Experts hopeful 35% of New Zealanders against jab will change their minds (Mike Hosking Breakfast, 2021)
Dr Kylie Quinn (current RMIT, Melbourne, Australia)
Dr Lisa Connor (currently Senior 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)
