The Cockburn Group - Malaria Immunology

Prof Ian Cockburn Group 2023

The focus of our research is understanding how to generate effective immunity against the malaria parasite Plasmodium. Malaria kills from 500,000 to 1 million people each year. A game-changer in the fight against malaria would be an effective vaccine. We know that two of the most effective branches of the immune system capable of fighting malaria are antibodies (which are made by B cells) and CD8+ T cells. Antibodies can block parasites in the blood as they travel from the site of the infectious mosquito bite to the liver, where the infection is first established. CD8+ T cells are specialized killers that can patrol the liver, and find and eliminate the Plasmodium-infected cells. If we can understand how to harness these responses properly, we might be able to develop vaccines capable of giving robust and durable protection against malaria.

Accordingly, research in my group is focused on the 2 broad areas of B cell responses to malaria and T cell responses to malaria. We are always on the look out for good students Domestically and Internationally with scholarships available. Please see our potential project opportunities on this page. 

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A multimorphic mutation in IRF4 causes human autosomal dominant combined immunodeficiency. Science immunology
2023-01-20 | journal-article

PMID: 36662884
DOI: 10.1126/sciimmunol.ade7953  

T follicular helper 17 (Tfh17) cells are superior for immunological memory maintenance.
eLife
2023-01-19 | journal-article

PMID: 36655976
PMC: PMC9891720 DOI: 10.7554/elife.82217  

Housebreaking Plasmodium parasites leave their fingerprints at the door.
Trends in parasitology
2022-09-23 | journal-article

PMID: 36163104
DOI: 10.1016/j.pt.2022.09.005  

The development and function of CD11c+ atypical B cells - insights from single cell analysis. Frontiers in immunology
2022-08-22 | journal-article

PMID: 36072594
PMC: PMC9441955
DOI: 10.3389/fimmu.2022.979060  

Innate immunity to malaria: The good, the bad and the unknown.
Frontiers in immunology
2022-08-19 | journal-article

PMID: 36059493
PMC: PMC9437427
DOI: 10.3389/fimmu.2022.914598  

Interactions with Asialo-Glycoprotein Receptors and Platelets Are Dispensable for CD8<sup>+</sup> T Cell Localization in the Murine Liver.
Journal of immunology (Baltimore, Md. : 1950) 2022-06-01 | journal-article

PMID: 35649630
DOI: 10.4049/jimmunol.2101037  

A New Method Based on the von Mises-Fisher Distribution Shows that a Minority of Liver-Localized CD8 T Cells Display Hard-To-Detect Attraction to <i>Plasmodium</i>-Infected Hepatocytes.
Frontiers in bioinformatics
2022-01-31 | journal-article
PMID: 36303744
PMC: PMC9580869
DOI: 10.3389/fbinf.2021.770448

Extrafollicular Plasmablasts Present in the Acute Phase of Infections Express High Levels of PD-L1 and Are Able to Limit T Cell Response
Frontiers in Immunology

2022 | journal-article
DOI: 10.3389/fimmu.2022.828734 EID: 2-s2.0-85131270707
Part of ISSN: 16643224

Mathematical modeling suggests that a single Plasmodium-specific CD8 T cell can eliminate a malaria liver stage in mice
bioRxiv
2022 | other
DOI: 10.1101/2022.05.18.492520
EID: 2-s2.0-85133248114
Part of ISSN: 26928205

Splenic Dendritic Cells and Macrophages Drive B Cells to Adopt a Plasmablast Cell Fate
Frontiers in Immunology
2022 | journal-article

DOI: 10.3389/fimmu.2022.825207 EID: 2-s2.0-85128779309
Part of ISSN: 16643224

Avid binding by B cells to the Plasmodium circumsporozoite protein repeat suppresses responses to protective subdominant epitopes.
Cell reports
2021-04-01 | journal-article
DOI: 10.1016/j.celrep.2021.108996
EID: 2-s2.0-85104052888
Part of ISSN: 22111247
DOI: 10.1101/2020.01.12.903682
EID: 2-s2.0-85095512659
Part of ISSN: 26928205
PMID: 33852850
PMC: PMC8052187
 

A Point Mutation in IKAROS ZF1 Causes a B Cell Deficiency in Mice.
Journal of immunology (Baltimore, Md. : 1950) 2021-03-03 | journal-article

PMID: 33658297
DOI: 10.4049/jimmunol.1901464  

The challenges of a circumsporozoite protein-based malaria vaccine.
Expert review of vaccines
2021-02-07 | journal-article

PMID: 33554669
DOI: 10.1080/14760584.2021.1874924  

Atypical B cells are part of an alternative lineage of B cells that participates in responses to vaccination and infection in humans.
Cell reports

2021-02-01 | journal-article
PMID: 33567273
DOI: 10.1016/j.celrep.2020.108684  

A Dual-Antigen Enzyme-Linked Immunosorbent Assay Allows the Assessment of Severe Acute Respiratory Syndrome Coronavirus 2 Antibody Seroprevalence in a Low-Transmission Setting
The Journal of infectious diseases

2021 | journal-article
DOI: 10.1093/infdis/jiaa623
EID: 2-s2.0-85099043628
Part of ISSN: 15376613
 

Development of Plasmodium-specific liver-resident memory CD8<sup>+</sup> T cells after heat-killed sporozoite immunization in mice
European Journal of Immunology

2021 | journal-article
DOI: 10.1002/eji.202048757
EID: 2-s2.0-85100988997
Part of ISSN: 15214141 00142980  

Dysregulation of PAX5 causes uncommitted B cell development and tumorigenesis in mice
bioRxiv
2021 | other

DOI: 10.1101/2021.01.29.428877 EID: 2-s2.0-85103803444
Part of ISSN: 26928205

Platelets are dispensable for the ability of CD8+ T cells to accumulate, patrol, kill and reside in the liver
bioRxiv
2021 | other

DOI: 10.1101/2021.11.09.467964 EID: 2-s2.0-85121366487
Part of ISSN: 26928205

Prevalence of asymptomatic SARS-CoV-2 infection in elective surgical patients in Australia: a prospective surveillance study
ANZ Journal of Surgery

2021 | journal-article
DOI: 10.1111/ans.16564
EID: 2-s2.0-85099024714
Part of ISSN: 14452197 14451433  

Resident T cells seek the perfect place to work from home
Nature Immunology
2021 | journal-article

DOI: 10.1038/s41590-021-01003-2 EID: 2-s2.0-85113358958
Part of ISSN: 15292916 15292908  

A dual antigen ELISA allows the assessment of SARS- CoV-2 antibody seroprevalence in a low transmission setting
medRxiv

2020 | other
DOI: 10.1101/2020.09.09.20191031 EID: 2-s2.0-85099084229  

A Natural Peptide Antigen within the Plasmodium Ribosomal Protein RPL6 Confers Liver T<inf>RM</inf> Cell-Mediated Immunity against Malaria in Mice
Cell Host and Microbe

2020 | journal-article
DOI: 10.1016/j.chom.2020.04.010 EID: 2-s2.0-85085278821
Part of ISSN: 19346069 19313128  

A new method based on the von Mises-Fisher distribution shows that a minority of liver-localized CD8 T cells display hard-to-detect attraction to Plasmodium- infected hepatocytes
bioRxiv
2020 | other
DOI: 10.1101/2020.12.12.422451
EID: 2-s2.0-85128000109
Part of ISSN: 26928205

A Potent Anti-Malarial Human Monoclonal Antibody Targets Circumsporozoite Protein Minor Repeats and Neutralizes Sporozoites in the Liver
Immunity

2020 | journal-article
DOI: 10.1016/j.immuni.2020.08.014 EID: 2-s2.0-85091951261
Part of ISSN: 10974180 10747613  

Antibody Feedback Limits the Expansion of B Cell Responses to Malaria Vaccination but Drives Diversification of the Humoral Response
Cell Host and Microbe

2020 | journal-article
DOI: 10.1016/j.chom.2020.07.001 EID: 2-s2.0-85089297655
Part of ISSN: 19346069 19313128  

Atypical B cells are a normal component of immune responses to vaccination and infection in humans
bioRxiv
2020 | other

DOI: 10.1101/2020.05.28.120808 EID: 2-s2.0-85098896662
Part of ISSN: 26928205

Liver environment-imposed constraints diversify movement strategies of liver-localized CD8 T cells
bioRxiv
2020 | other

DOI: 10.1101/2020.11.06.371690 EID: 2-s2.0-85117429271
Part of ISSN: 26928205
 

Malaria exposure drives both cognate and bystander human B cells to adopt an atypical phenotype European Journal of Immunology
2020 | journal-article

DOI: 10.1002/eji.201948473
EID: 2-s2.0-85085076867
Part of ISSN: 15214141 00142980  

PD-L1hi plasmablasts limit the T cell response during the acute phase of parasite infections bioRxiv
2020 | other
DOI: 10.1101/2020.06.10.142067
EID: 2-s2.0-85098893833
Part of ISSN: 26928205
 

Antibody feedback limits the expansion of cognate memory B cells but drives the diversification of vaccine- induced antibody responses
bioRxiv
2019 | other
DOI: 10.1101/808543
EID: 2-s2.0-85095639540
Part of ISSN: 26928205
 

Clustering of Activated CD8 T Cells Around Malaria- Infected Hepatocytes Is Rapid and Is Driven by Antigen- Specific Cells
Frontiers in Immunology

2019 | journal-article
DOI: 10.3389/fimmu.2019.02153 EID: 2-s2.0-85072973536
Part of ISSN: 16643224
 

Erratum: Liver-Resident Memory CD8+ T Cells Form a Front-Line Defense against Malaria Liver- Stage Infection (Immunity (2016) 45(4) (889–902), (S1074761316303351), (10.1016/j.immuni.2016.08.011)) Immunity

2019 | journal-article
DOI: 10.1016/j.immuni.2019.09.019 EID: 2-s2.0-85072756144
Part of ISSN: 10974180 10747613  

Clustering of activated CD8 T cells around malaria- infected hepatocytes is rapid and is driven by antigen- specific T cells
bioRxiv

2018 | other
DOI: 10.1101/508796
EID: 2-s2.0-85095636737
Part of ISSN: 26928205
 

HIV Immunogens: Affinity Is Key
Immunity

2018 | journal-article
DOI: 10.1016/j.immuni.2018.01.002 EID: 2-s2.0-85044854734
Part of ISSN: 10974180 10747613  

Malaria prevention: from immunological concepts to effective vaccines and protective antibodies
Nature Immunology
2018 | journal-article

DOI: 10.1038/s41590-018-0228-6 EID: 2-s2.0-85055126938
Part of ISSN: 15292916 15292908  

Adaptive immunity to Plasmodium blood stages

Malaria: Immune Response to Infection and Vaccination

2017 | book
Part of DOI: 10.1007/978-3-319-45210-4_3 EID: 2-s2.0-85028870178
 

Cationic amino acid transporters play key roles in the survival and transmission of apicomplexan parasites Nature Communications
2017 | journal-article

DOI: 10.1038/ncomms14455
EID: 2-s2.0-85013170822
Part of ISSN: 20411723
 

Embracing diversity gives antibodies the power to bind

Immunology and Cell Biology

2017 | journal-article
DOI: 10.1038/icb.2017.75
EID: 2-s2.0-85034584161
Part of ISSN: 14401711 08189641  

Flexible polygon-mirror based laser scanning microscope platform for multiphoton in-vivo imaging Journal of Biophotonics
2017 | journal-article
DOI: 10.1002/jbio.201600289
EID: 2-s2.0-85013103914
Part of ISSN: 18640648 1864063X
 

T-dependent B cell responses to Plasmodium induce antibodies that form a high-avidity multivalent complex with the circumsporozoite protein
PLoS Pathogens

2017 | journal-article
DOI: 10.1371/journal.ppat.1006469 EID: 2-s2.0-85026888674
Part of ISSN: 15537374 15537366  

TFH-derived dopamine accelerates productive synapses in germinal centres Nature
2017 | journal-article

DOI: 10.1038/nature23013
EID: 2-s2.0-85025136766
Part of ISSN: 14764687 00280836  

Up-regulation of LFA-1 allows liver-resident memory T cells to patrol and remain in the hepatic sinusoids Science Immunology
2017 | journal-article

DOI: 10.1126/sciimmunol.aaj1996 EID: 2-s2.0-85021411984
Part of ISSN: 24709468
 

Adenosine monophosphate deaminase 3 activation shortens erythrocyte half-life and provides malaria resistance in mice
Blood

2016 | journal-article
DOI: 10.1182/blood-2015-09-666834 EID: 2-s2.0-84995677797
Part of ISSN: 15280020 00064971  

Chemically attenuated blood-stage Plasmodium yoelii parasites induce long-lived and strain-transcending protection
Infection and Immunity

2016 | journal-article
DOI: 10.1128/IAI.00157-16
EID: 2-s2.0-84979741940  

Dendritic cell function and antigen presentation in malaria
Current Opinion in Immunology
2016 | journal-article

DOI: 10.1016/j.coi.2016.01.010 EID: 2-s2.0-84956604985  

High speed multiphoton imaging

Proceedings of SPIE - The International Society for Optical Engineering
2016 | conference-paper
DOI: 10.1117/12.2242951

EID: 2-s2.0-85011422031
Part of ISSN: 1996756X 0277786X  

Liver-Resident Memory CD8+ T Cells Form a Front-Line Defense against Malaria Liver-Stage Infection
Immunity

2016 | journal-article
DOI: 10.1016/j.immuni.2016.08.011 EID: 2-s2.0-84994876821  

Lymph-Node Resident CD8+ Dendritic Cells Capture Antigens from Migratory Malaria Sporozoites and Induce CD8+ T Cell Responses
PLoS Pathogens

2015 | journal-article
DOI: 10.1371/journal.ppat.1004637 EID: 2-s2.0-84924390082  

Studying the effect of chloroquine on sporozoite- induced protection and immune responses in Plasmodium berghei malaria
Malaria Journal

2015 | journal-article
DOI: 10.1186/s12936-015-0626-2 EID: 2-s2.0-84926453425  

Antibody and B cell responses to Plasmodium sporozoites
Frontiers in Microbiology
2014 | journal-article

DOI: 10.3389/fmicb.2014.00625 EID: 2-s2.0-84987845540  

CD8+ T cells eliminate liver-stage Plasmodium berghei parasites without detectable bystander effect
Infection and Immunity

2014 | journal-article
DOI: 10.1128/IAI.01500-13
EID: 2-s2.0-84896467579  

Classification of T cell movement tracks allows for prediction of cell function
International Journal of Computational Biology and Drug Design

2014 | journal-article
DOI: 10.1504/IJCBDD.2014.061655 EID: 2-s2.0-84901923406  

The chemokine receptor CXCR6 is required for the maintenance of liver memory CD8+ T cells specific for infectious pathogens
Journal of Infectious Diseases

2014 | journal-article
DOI: 10.1093/infdis/jiu281
EID: 2-s2.0-84922042365  

Chimeric parasites as tools to study Plasmodium immunology and assess malaria vaccines. Methods in molecular biology (Clifton, N.J.)
2013 | journal-article

EID: 2-s2.0-84873019233  

In vivo imaging of CD8+ T cell-mediated elimination of malaria liver stages
Proceedings of the National Academy of Sciences of the United States of America

2013 | journal-article
DOI: 10.1073/pnas.1303858110 EID: 2-s2.0-84878424315  

Looking under the skin: The first steps in malarial infection and immunity
Nature Reviews Microbiology
2013 | journal-article

DOI: 10.1038/nrmicro3111
EID: 2-s2.0-84884228351  

Unique transcriptional profile of liver-resident memory CD8+ T cells induced by immunization with malaria sporozoites
Genes and Immunity

2013 | journal-article
DOI: 10.1038/gene.2013.20
EID: 2-s2.0-84880923153  

CD4+ T cells modulate expansion and survival but not functional properties of effector and memory CD8+ T cells induced by malaria sporozoites

PLoS ONE

2011 | journal-article
DOI: 10.1371/journal.pone.0015948 EID: 2-s2.0-79251535587  

Dendritic cells and hepatocytes use distinct pathways to process protective antigen from Plasmodium in vivo PLoS Pathogens
2011 | journal-article

DOI: 10.1371/journal.ppat.1001318 EID: 2-s2.0-79953268563  

CpG-enhanced CD8+ T-cell responses to peptide immunization are severely inhibited by B cells European Journal of Immunology
2010 | journal-article

DOI: 10.1002/eji.200939493
EID: 2-s2.0-74249083537  

Prolonged antigen presentation is required for optimal CD8+ T cell responses against malaria liver stage parasites.
PLoS pathogens

2010 | journal-article
EID: 2-s2.0-77955930820  

B7-H1 blockade increases survival of dysfunctional CD8+ T cells and confers protection against Leishmania donovaniinfections
PLoS Pathogens

2009 | journal-article
DOI: 10.1371/journal.ppat.1000431 EID: 2-s2.0-67249117672
 

Memory CD8+ T cell responses expand when antigen presentation overcomes T cell self- regulation
Journal of Immunology

2008 | journal-article
DOI: 10.4049/jimmunol.180.1.64 EID: 2-s2.0-40449116443
 

Platelet Factor 4 Mediates Inflammation in Experimental Cerebral Malaria
Cell Host and Microbe
2008 | journal-article

DOI: 10.1016/j.chom.2008.07.003 EID: 2-s2.0-48649098063  

Protective CD8+ T cells against Plasmodium liver stages: Immunobiology of an 'unnatural' immune response
Immunological Reviews

2008 | journal-article
DOI: 10.1111/j.1600-065X.2008.00671.x EID: 2-s2.0-52049105157
 

CD8+ T lymphocytes protective against malaria liver stages are primed in skin-draining lymph nodes
Nature Medicine

2007 | journal-article
DOI: 10.1038/nm1628
EID: 2-s2.0-34548276242  

T cell memory in malaria
Current Opinion in Immunology

2007 | journal-article
DOI: 10.1016/j.coi.2007.05.008 EID: 2-s2.0-34548019006  

Erythrocyte complement receptor 1 (CR1) expression level is not associated with polymorphisms in the promoter or 3′ untranslated regions of the CR1 gene
International Journal of Immunogenetics

2006 | journal-article
DOI: 10.1111/j.1744-313X.2005.00552.x EID: 2-s2.0-33645071588

Protective and pathogenic roles of CD8+ T cells during malaria infection
Parasite Immunology
2006 | journal-article

DOI: 10.1111/j.1365-3024.2006.00777.x EID: 2-s2.0-33644863805
 

Protective CD8+ T cells induced by malaria sporozoites do not undergo modulation of interleukin-7 receptor expression
Infection and Immunity

2006 | journal-article
DOI: 10.1128/IAI.74.4.2495-2497.2006 EID: 2-s2.0-33645510077
 

Virulence of malaria is associated with differential expression of Plasmodium falciparum var gene subgroups in a case-control study
Journal of Infectious Diseases

2006 | journal-article
DOI: 10.1086/503776
EID: 2-s2.0-33646931473  

A complement receptor-1 polymorphism with high frequency in malaria endemic regions of Asia but not Africa
Genes and Immunity

2005 | journal-article
DOI: 10.1038/sj.gene.6364150
EID: 2-s2.0-13844320382  

IL-4 receptor expression on CD8+ T cells is required for the development of protective memory responses against liver stages of malaria parasites Journal of Experimental Medicine

2005 | journal-article
DOI: 10.1084/jem.20042463
EID: 2-s2.0-23944434020  

A human complement receptor 1 polymorphism that reduces Plasmodium falciparum rosetting confers protection against severe malaria
Proceedings of the National Academy of Sciences of the United States of America

2004 | journal-article
DOI: 10.1073/pnas.0305306101 EID: 2-s2.0-0345827588
 

A simple method for accurate quantification of complement receptor 1 on erythrocytes preserved by fixing or freezing
Journal of Immunological Methods
2002 | journal-article
DOI: 10.1016/S0022-1759(02)00368-X
EID: 2-s2.0-0037146792
 

Erythrocyte CR1 expression level does not correlate with a HindIII restriction fragment length polymorphism in Africans; implications for studies on malaria susceptibility
Genes and Immunity
2002 | journal-article
DOI: 10.1038/sj.gene.6363899
EID: 2-s2.0-19044382790

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