Complex dynamics of natural acquisition of host immune responses to P. falciparum and P.vivax in PNG
Project type
PhD
| Supervisor(s) | Division | |
| (Primary) | Infection and Immunity | .(JavaScript must be enabled to view this email address) |
| (Co-supervisor) | Infection and Immunity | .(JavaScript must be enabled to view this email address) |
Details of project
Complex dynamics of natural acquisition of host immune responses to P. falciparum and P. vivax in PNG children. Under natural exposure, immunity to malaria is acquired over several years and in distinct ‘phases’: children first acquire immunity to severe and fatal disease and then, after several years of intense exposure, immunity to uncomplicated disease. Immunity to infection is acquired very slowly and remains imperfect even in adults. The speed of this process is substantially faster for P. vivax than P. falciparum.
The process of immune acquisition involves innate as well as adaptive humoral and cellular responses to a large range of antigenic targets, the exact nature and the interplay of which are yet poorly understood. Past studies of human immune responses to malaria have mostly concentrated either on one arm of the immune response, a limited set of antigenic targets or both and were often done in poorly designed field studies. In addition, immune measures were usually done at a single time point, even though responses are known to vary considerably over time.
For the past 7 years, we have been undertaking an in-depth assessment of different aspects of the immune response to whole parasites and a wide spectrum of antigens antigens in a series of detailed longitudinal cohort studies in Papua New Guinea children. The resulting sample and datasets now allow in-depth analyses of the complex, longitudinal dynamics of immune responses and their association with protective immunity in PNG childre.
Project goals:
- Investigate the relationship between different aspects of host immune responses (cellular and humoral) to P. falciparum.
- Determine the longitudinal dynamics of antibody responses to P. falciparum and P. vivax and their relationships with infection and protective immunity.
Addressing the first goal will involve in-depth analyses of existing multivariate datasets that include a large array of cellular and humoral immune responses to P. falciparum from a series of population-bases studies in children 1-10 yrs of age. For the second goal, we will use existing samples sets from 2 cohorts in children 1-5 years to repeatedly measure antibody responses to a varienty of P. falciparum and P. vivax antigens using a robotics-based high-througput ELISA assay. We will then apply advanced longitudinal statistical models to the resulting data to investigate how age and exposure to malaria infection affect the dynamics of antibody responses and their association with incidence of clinical malaria.
At a later stage these models can then be applied to other longitdunal data sets of antibody responses in children under 2 yrs and from 5-10yrs. As an immune-epidemiology project dealing with highly parameterised, longitudinal datasets this project is best suited for a candidate with a background/interest in epidemiology and biostatics, who is keen to learn about malaria immunology and combine analytical and laboratory approaches.
Project references
- Schofield L and Mueller I. Clinical immunity to malaria. Curr Mol Med. 2006 6:205-221.
- Lin E, et al. Differential patterns of infection and disease with P. falciparum and P. vivax in young Papua New Guinean children. PLoS One. 2010 5:e9047.
- Michon P, et al. The risk of malarial infections and disease in Papua New Guinean children. Am J Trop Med Hyg. 2007 76:997-1008.
- Robinson LJ, et al. Cellular TNF, IFN-{gamma} and IL-6 responses: correlates of immunity and risk of clinical Plasmodium falciparum malaria in children from Papua New Guinea. Infect Immun. 2009 77:3033-3043.
- Stanisic DI, et al. Immunoglobulin G subclass-specific responses against Plasmodium falciparum merozoite antigens are associated with control of parasitemia and protection from symptomatic illness. Infect Immun. 2009 77:1165-1174.
- Richards JS, et al. Naturally-acquired antibodies to erythrocyte binding antigens of Plasmodium falciparum are associated with protection from malaria and high density parasitemia. Clin Infect Dis. 2010 51:e50-60.
- Akpogheneta OJ, Dunyo S, Pinder M and Conway DJ. Boosting antibody responses to Plasmodium falciparum merozoite antigens in children with highly seasonal exposure to infection. Parasite Immunol. 2010 296-304.
Research interests
Despite impressive recent gains in the global fight to control malaria, the disease continues to be a major burden on people in endemic countries. To date, it is estimated that 2.4 and 2.8 million people worldwide are at risk of contracting P. falciparum and P. vivax, respectively.
Our lab aims to contribute to further, sustainable gains in our fight against malaria. We are conducting population-based malaria studies that are locally relevant for the control and eventual elimination of malaria from affected populations in the Asia-Pacific region and beyond. The population-based malaria research program of our group aims to bridge basic Plasmodium biology and clinical development of new interventions to control and eventually eliminate malaria.
To that effect the research is focused around three main ‘themes’:
- the comparative biology of P. falciparum and P. vivax host-parasite interactions;
- the (clinical) epidemiology and intervention research in Papua New Guinea; and
- evaluation of the impact of intensified malaria control programs on malaria burden and host-vector-parasite interaction.
Answering complex problems regarding host-vector-parasite interactions requires highly integrated, multidisciplinary approaches. Our research program draws on diverse scientific disciplines ranging from molecular parasitology, host genetic adaptations and immune responses, clinical, epidemiological and population-based research, curative and preventative interventions to research on health systems, monitoring and evaluation, and social aspects of malaria.
A special focus lies in studying the P. vivax host-parasite interaction and our group is recognised as one of the best in studying the epidemiology of P. vivax. For further details of the project undertaken by the lab see: http://www.wehi.edu.au/faculty_members/professor_ivo_mueller
Research theme
Cancer
Scientific discipline
- Immunology
- Microbiology
- Statistics
Keywords
P. falciparum, P.vivax,cellular immunity, humoral immunity, multivariate analyses, longitudinal analyses, population-based study