Biomarkers

Blood levels of immune cell markers and antibodies could help predict protective responses to Plasmodium CSP-based malaria vaccines. A cohort of 46 healthy volunteers received one of two malaria vaccine regimens before challenge with P. falciparum and had blood samples taken at baseline and after each dose of vaccine to monitor immune responses, and after challenge to test for parasitemia. In 25 volunteers immunized with three doses of RTS,S vaccine, the absence of detectable parasitemia was associated with high pre-challenge titers of CSP-specific antibodies, high expression of B cell gene signatures in peripheral blood mononuclear cells (PBMCs) after each dose and low expression levels of NK cell gene signatures in PBMCs after the third dose. In 21 volunteers receiving a priming dose of an adenoviral vaccine encoding parasitic CSP followed by two boosting doses of RTS,S, the absence of detectable parasitemia was associated with a high frequency of activated, CSP-specific CD4⁺ T cells two weeks after the priming dose; high expression of dendritic cell gene expression signatures in PBMCs after the priming and the first RTS,S doses; and low expression of NK cell activation gene expression signatures in PBMCs after each dose. Next steps could include validating the markers in larger cohorts of volunteers immunized with RTS,S or other CSP-based vaccines.

GlaxoSmithKline plc has RTS,S vaccine (Mosquirix; GSK257049), a recombinant protein-based malaria vaccine targeting the CSP sequence of P. falciparum combined with the AS01 adjuvant, in registration to prevent malaria...