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The development of an efficacious vaccine against the Plasmodium parasite remains a top priority. Previous research has demonstrated the ability of a prime-boost virally vectored sub-unit vaccination regimen, delivering the liver-stage expressed malaria antigen TRAP, to produce high levels of antigen-specific T cells. The liver-stage of malaria is the main target of T cell-mediated immunity, yet a major challenge in assessing new T cell inducing vaccines has been the lack of a suitable pre-clinical assay. We have developed a flow-cytometry based in vitro T cell killing assay using a mouse hepatoma cell line, Hepa1-6, and Plasmodium berghei GFP expressing sporozoites. Using this assay, P. berghei TRAP-specific CD8+ T cell enriched splenocytes were shown to inhibit liver-stage parasites in an effector-to-target ratio dependent manner. Further development of this assay using human hepatocytes and P. falciparum would provide a new method to pre-clinically screen vaccine candidates and to elucidate mechanisms of protection in vitro.

Original publication

DOI

10.1371/journal.pone.0119880

Type

Journal article

Journal

PLoS One

Publication Date

2015

Volume

10

Keywords

Animals, Antigens, Protozoan, CD8-Positive T-Lymphocytes, Cell Line, Female, Green Fluorescent Proteins, Humans, In Vitro Techniques, Liver, Malaria, Malaria Vaccines, Mice, Mice, Inbred C57BL, Plasmodium berghei, Protozoan Proteins, Spleen, Sporozoites