Ex vivo lymphocyte phenotyping during Plasmodium falciparum sporozoite immunization in humans

Immunization of malaria-naive volunteers under chemoprophylaxis with Plasmodium falciparum sporozoites (CPS) efficiently and reproducibly induces sterile protection and thus constitutes an excellent model to study protective immune responses against malaria. Here, we performed the first longitudinal assessment of lymphocyte activation and differentiation kinetics during sporozoite immunization in 15 volunteers by exvivo lymphocyte flow cytometry analysis. Both CD4 and CD8 T cells as well as T cells, NK cells and CD3+ CD56+ cells showed increased activation and proliferation following immunization. Transient induction of the transcription factor T-bet and the cytotoxic molecule granzyme B indicated a role of Th1 responses and cytotoxic T cells in CPS-induced immunity. The absolute number of T cells as well as the proportion of granzyme B-containing T cells showed a significant and sustained increase. Regulatory T-cell (Treg) proliferation was significantly higher after the second immunization in subjects subsequently not protected against challenge infection. These findings indicate an important role for T cells, Th1 and cytotoxic responses in whole sporozoite immunization with a possibly suppressive role of Tregs.