LAUSR

Sporozoite-based approaches currently represent the most effective vaccine strategies for induction of sterile protection against Plasmodium falciparum (Pf) malaria. Clinical development of sub-unit vaccines is almost exclusively centered around the Circum-sporozoite Protein (CSP) an abundantly expressed protein on the sporozoite membrane. Anti-CSP antibodies are able to block sporozoite invasion and development in human hepatocytes and subsequently prevent clinical malaria.Here we investigated whether sporozoite-induced human antibodies with specificities different from CSP can reduce Pf-liver stage development. IgG preparations were obtained from 12 volunteers inoculated with a protective immunization regime of whole-sporozoites under chloroquine prophylaxis. These IgGs were depleted for CSP-specificity by affinity chromatography. Recovered non-CSP antibodies were tested for sporozoite membrane binding and for functional inhibition of sporozoite invasion of a human hepatoma cell line and hepatocytes both in vitro and in vivo. Post-immunization IgGs depleted for CSP-specificity of 9 out of 12 donors recognized sporozoite surface antigens. Samples from 5 out of 12 donors functionally reduced parasite-liver cell invasion or development using the hepatoma cell line HC-04 and FRG-huHep mice containing human liver cells.The combined data provide clear evidence that non-CSP proteins as yet undefined do represent antibody targets for functional immunity against Plasmodium falciparum parasites responsible for malaria.