Last Updated: 28/05/2025
Evaluation of Novel Preerythrocytic Anti-infection Malaria Vaccine Candidates
Objectives
The main objective of this project is to identify novel candidate pre-erythrocytic vaccine antigens (PEVA) that could add to the level of protection achieved with CSP immunogens alone. More specifically, to determine fine antigen (Ag) specificities of CD8 T cells that target liver stages (LS) malaria parasites. Guided by algorithms for predicting MHC class I-restricted epitopes, we ranked sequences of 32 Pb LS Ags and selected 400 peptides restricted by mouse H-2Kb and H-2D balleles for analysis in the high-throughput method of caged MHC class I-tetramer technology.
Sterile protection against malaria infection can be induced by multiple exposures to radiation-attenuated sporozoite (RAS) parasite forms in mice and humans if the RAS remain sufficiently viable to invade hepatocytes. Manufacturing of RAS has several technical hurdles to overcome to allow mass immunization, and therefore, subunit vaccines have been the primary focus of development in recent decades. RTS,S based on Pf circumsporozoite protein (PfCSP), the predominant sporozoite surface antigen, is the most advanced subunit candidate but has shown only limited efficacy against malaria episodes in Phase III testing. Thus, new subunit vaccine strategies are needed. CSP tolerant transgenic mice are also protected after RAS immunization, implicating additional pre-erythrocytic antigens as targets of sterile immunity.
Jan 2010 — Jan 2019
$4.4M
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