Last Updated: 16/02/2023
Age-dependent diversity of innate immune responses in malaria
Objectives
To evaluate the impact of age on innate immune responses in children and adults during acute infection with malaria and after recovery.
An individual’s immune system changes with age and exposure to different environmental pathogens. In malaria, naturally acquired immunity is dependent on both the individual’s age and exposure to the parasite. In addition, age may also affect vaccine-induced immunity, possibly accounting for the fact that the only available malaria vaccine to-date has been less effective in children in malaria-endemic areas than was demonstrated in malaria-naive adults in volunteer infection studies. Despite this, the relationship between age and the function of innate immune cells in malaria remains poorly understood.
Innate immune cells are essential to identifying invading, foreign pathogens (such as the malaria parasite) as well as harnessing the immune system to combat disease. These innate cells make up a large proportion of our immune system, yet our current understanding of their function in human malaria is limited. To address this, we will examine the changes in gene expression of an essential innate cell subset (monocyte) during malaria infection. We will use novel cutting-edge technologies to analyse specific innate cells from malaria patients and to quantify changes to this essential cell subset during and after malaria. An increased understanding of the impact of age on the innate immune response will be necessary to improve future vaccine outcomes.
We will utilise existing clinical samples collected from the low transmission setting of Sabah, Malaysia by co-investigators Grigg, Barber and William. Within this low transmission setting, both children (7-16 years) and adults (18-55 years) remain susceptible to clinical disease due to the lack of naturally acquired immunity. As such, age dependent differences to malaria can be investigated in this cohort. PBMCs were collected from participants who were enrolled with consent in the prospective comparative studies of different Plasmodium species, at acute infection (day 0), day 7 and day 28 after treatment. P. falciparum malaria was confirmed by PCR10.
Nov 2019 — Oct 2023
$15,000
