Authors

S G Thorburn¹; S U Khan³; K MatuschewskiJ C Hafalla¹;  ¹ London School of Hygiene and Tropical Medicine;  ² Max Planck Institute for Infection Biology, Germany;  ³ University College London

Discussion

Sterile protection from malaria through multiple attenuated sporozoite immunisations has been shown to be dependent on T cells and antibodies in mouse and human studies. Understanding these protective mechanisms is crucial in the future development of novel vaccines. Currently, CD8 T cell regulation mechanisms are not well understood in pre-erythrocytic malaria. This research investigated two co-inhibitory receptors that have been shown to influence CD8 T cell proliferation and activation. C57BL/6 mice were given one attenuated Plasmodium berghei sporozoite immunisation concurrently with antibody blockade of cytotoxic T lymphocyte antigen 4 (CTLA4) or programmed death ligand 1 (PDL1). PDL1 blockade led to parasitaemia in all mice under these conditions. CTLA4 blockade however increased the likelihood of sterile protection with sporozoite challenge as well as increasing the frequency of specific effector CD8 T cells. This is proof of principle that blockade of certain negative regulators of CD8 T cell activation can augment parasite specific responses after a normally non-protective single whole sporozoite immunisation and provide improved vaccine efficacy.