Glutamate-rich protein (GLURP) induces antibodies that inhibit in vitro growth of Plasmodium falciparum in a phase 1 malaria vaccine trial

The glutamate-rich protein (GLURP) of P. falciparum is the target of cytophilic antibodies which are significantly associated with protection against clinical malaria. A phase 1 clinical trial was conducted in healthy adult volunteers with the long synthetic peptide (LSP) GLURP85–213 combined with either Aluminum Hydroxide (Alum, 18 volunteers) or Montanide ISA 720 (ISA, 18 volunteers) as adjuvants. Immunizations with 10, 30 or 100 μg GLURP85–213 were administered subcutaneously at days 0, 30, and 120.Adverse events occurred more frequently with increasing dosage of GLURP85–213 LSP and were more prevalent in the ISA group. Serious vaccine-related adverse events were not observed.The vaccine induced dose-dependent cellular and humoral immune responses, with high levels of (mainly cytophilic IgG1) antibodies that recognize parasites by immunofluorescence (IFA). Plasma samples collected 30 days after the last immunization induced a dose-dependent inhibition of parasite growth in vitro in the presence of monocytes. In conclusion, immunizations with GLURP85–213 LSP formulations induce adverse events but can be administered safely, generating antibodies with capacity to mediate growth-inhibitory activity against P. falciparum in vitro.