Chua, Y. C.; Holz, L. E.; Fernandez-Ruiz, D.; Draper, S. L.; Anderson, R. J.; Compton, B. J.; Schittenhelm, R. B.; Cozijnsen, A.; Jennison, C.; Collier, S.; Steel, R. W. J.; Jayasinge, D.; Gras, S.; Boddey, J. A.; Purcell, A. W.; McFadden, G. I.; Hermans, I. F.; Painter, G. F.; Heath, W. R.

Vaccine-induced cytotoxic T cells can prevent malaria by killing parasite-infected hepatocytes during the liver stage. While several antigenic targets have been identified, little consideration has been given to their temporal expression. Here, we identified SERA1 of Plasmodium berghei as a late liver-stage target in rodent malaria and further showed that the classic vaccine antigen thrombospondin-related adhesion protein (TRAP) is only an early target. While vaccination with either antigen alone was modestly protective, combining these antigens enabled killing over the entire liver-stage, greatly improving efficacy. Given the relatively long liver-stage in human malaria, our findings imply TRAP-dependent vaccines likely utilize only a small proportion of the available liver-stage to eradicate parasites. Our findings further indicate that considerations of temporal coverage when selecting vaccine antigens will improve efficacy.