Abstract
Controlled human malaria infection (CHMI) using cryopreserved non-attenuated Plasmodium falciparum sporozoites (PfSPZ) offers a unique opportunity to investigate naturally acquired immunity ...(NAI). By analyzing blood samples from 5 malaria-naïve European and 20 African adults with lifelong exposure to malaria, before, 5, and 11 days after direct venous inoculation (DVI) with Sanaria
R
PfSPZ Challenge, we assessed the immunological patterns associated with control of microscopic and submicroscopic parasitemia. All (5/5) European individuals developed parasitemia as defined by thick blood smear (TBS), but 40% (8/20) of the African individuals controlled their parasitemia, and therefore remained thick blood smear-negative (TBS
−
Africans). In the TBS
−
Africans, we observed higher baseline frequencies of CD4
+
T cells producing interferon-gamma (IFNγ) that significantly decreased 5 days after PfSPZ DVI. The TBS
−
Africans, which represent individuals with either very strong and rapid blood-stage immunity or with immunity to liver stages, were stratified into subjects with sub-microscopic parasitemia (TBS
-
PCR
+
) or those with possibly sterilizing immunity (TBS
−
PCR
−
). Higher frequencies of IFNγ
+
TNF
+
CD8
+
γδ T cells at baseline, which later decreased within five days after PfSPZ DVI, were associated with those who remained TBS
−
PCR
−
. These findings suggest that naturally acquired immunity is characterized by different cell types that show varying strengths of malaria parasite control. While the high frequencies of antigen responsive IFNγ
+
CD4
+
T cells in peripheral blood keep the blood-stage parasites to a sub-microscopic level, it is the IFNγ
+
TNF
+
CD8
+
γδ T cells that are associated with either immunity to the liver-stage, or rapid elimination of blood-stage parasites.
