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Granzyme B exhibits intrinsic antimalarial activity against Plasmodium falciparum, which is enhanced up to 8-fold when targeted to infected erythrocytes using a novel single-chain Fv fusion protein. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.ESTABLISHES_NEW_DIRECTION.

October 14, 2014Open Access

Antimalarial Activity of Granzyme B and Its Targeted Delivery by a Granzyme B–Single-Chain Fv Fusion Protein

SKStephanie KapelskiJanssen (Belgium)MAMelanie de AlmeidaResearch Institute of Molecular Pathology RFRainer FischerKarlsruhe Institute of Technology

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Abstract

We present here the first evidence that granzyme B acts against Plasmodium falciparum (50% inhibitory concentration IC50, 1,590 nM; 95% confidence interval 95% CI, 1,197 to 2,112 nM). We created a novel antimalarial fusion protein consisting of granzyme B fused to a merozoite surface protein 4 (MSP4)-specific single-chain Fv protein (scFv), which targets the enzyme to infected erythrocytes, with up to an 8-fold reduction in the IC50 (176 nM; 95% CI, 154 to 202 nM). This study confirms the therapeutic efficacies of recombinant antibody-mediated antimalarial immunotherapeutics based on granzyme B.

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