Immuno-biology of sexual stage antigens of Plasmodium falciparum parasites

Gametocytes of P. falciparum develop in 8-12 days while sequestered in the spleen or bone marrow; only mature gametocytes circulate peripherally. Artemisinin-based combination therapies (ACTs) reduce but do not eliminate gametocyte carriage, allowing some transmission to occur after treatment. Antibody responses shown to reduce malaria transmission to date are directed at the sexual stages in the mosquito, not those in the human host. The researchers have described distinct antibody responses recognising gametocytes and associated with reduced gametocyte carriage, but the target antigens are unknown. STEVOR are a candidate family of proteins encoded by a large cluster of stevor genes found in P. falciparum genome. These proteins are associated with erythrocyte membranes of red blood cells infected with immature gametocytes, contributing to rigidity and retention in sequestration sites. Disappearance of STEVOR from the erythrocyte membrane coincides with increased deformability and the subsequent release of fully mature gametocytes from sequestration sites. The hypothesis to be tested is that STEVOR antigens are targets of anti-gametocyte antibodies and that children with good anti-STEVOR humoral responses will present with low/no gametocytaemia. 

Basic Science
Genetics and Genomics
Immunology

Nov 2016 — Oct 2019

$213,095

Ghana