Malaria is a serious global health problem, with pregnant women and children particularly at risk.

Strategies to protect people against malaria by vaccination are critically dependent on understanding how the immune response occurs naturally. Individuals with life-long exposure to Plasmodium falciparum develop immunity that protects against severe malaria.

It has long been appreciated that IgG antibodies afford immune protection. However, the mechanisms by which antibodies protect remain uncertain. In particular, there is a paucity of studies investigating the interaction of antibody-opsonised parasites with the receptor for IgG: the Fc-gamma receptor (FcgR).

FcgRs are expressed by all leukocytes except T cells and play a critical role in pathogen clearance as well as modulating inflammatory responses.

This project aims to elucidate the cellular mechanisms by which FcgR balance pathogen clearance with inflammation. Human leukocyte subsets, which express different FcgR, are being characterised for their inflammatory and anti-parasite responses towards IgG-opsonised P. falciparum parasites.

Publications

2011

• Strain-transcending Fc-dependent killing of Plasmodium falciparum by merozoite surface protein 2 allele-specific human antibodies.
  Stubbs J, Olugbile S, Saidou B, Simpore J, Corradin G, Lanzavecchia A
  Infect Immun. 2011 Mar; 79(3):1143-1152

2006

• Alteration of the Fc gamma RIIa dimer interface affects receptor signaling but not ligand binding.
  Powell MS, Barnes NC, Bradford TM, Musgrave IF, Wines BD, Cambier JC, Hogarth P
  J Immunol. 2006 Jun; 176(12):7489-7494

2000

• Immunoglobulin G3 antibodies specific for the 19-kilodalton carboxyl-terminal fragment of Plasmodium yoelii merozoite surface protein 1 transfer protection to mice deficient in Fc-gammaRI receptors.
  Vukovic P, Hogarth PM, Barnes N, Kaslow DC, Good MF
  Infect Immun. 2000 May; 68(5):3019-3022