Abstract
While vaccines are central to eradicate malaria, they remain elusive, with numerous malaria vaccine candidates showing limited efficacy in Phase II and III studies. Controlled human malaria infection studies have showed that human volunteers, immunized with Plasmodium falciparum sporozoites under drug cover, were protected experimentally from a subsequent challenge. Here, to identify new targets associated with protection, we utilized a previously developed screening approach, where we screened sera from protected and non-protected individuals against newly included hypothetical antigens in a P. falciparum antigen library. PfVFT1 was found to be associated with protection, with antibodies against PfVFT1 being detected in all protected individuals. We found that vaccine-induced mouse anti-PfVFT sera inhibited parasite reinvasion into RBCs, promoted complement deposition to induce parasite lysis, and supported phagocytosis and antibody-dependent cellular inhibition of the parasite. Together, these data indicate that PfVFT1-specific antibodies can engage multiple effector mechanisms relevant to antimalarial immunity.
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Data Availability
The data generated in this study can be obtained upon reasonable request to the corresponding author. DNA sequences from 90 Thai field isolates are deposited in Genbank, and the Genbank accession numbers are PX636225 to PX636314, respectively.
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Acknowledgements
We thank Dr Jose-Juan Lopez-Rubio, University of Montpellier, France, for providing the CRISPR-Cas9 plasmids; Professor Zbynek Bozdech, Nanyang Technological University, Singapore, for providing the pBCam-3HA plasmid; Dr Simon Draper, Nuffield Department of Medicine, Jenner Institute, University of Oxford, UK, for providing the Rh5 antibodies; Professor Peter Preiser, School of Biological Sciences, Nanyang Technological University, Singapore, for providing the MSP1 antibodies. We also thank the FLOW facility at ID Labs and SIgN, A*STAR, Singapore for technical support with the cytometers. This work was funded by Agency for Science, Technology and Research (A*STAR) core grant. Shoklo Malaria Research Unit is part of the Mahidol Oxford University Research Unit, supported by the Wellcome Trust of Great Britain.
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Y.S.G. and L.R. conceived the study and wrote the paper. Y.S.G. designed the experiments. Y.S.G., H.M., P.X.H. and C.Y.L. performed the experiments. Y.S.G., H.M., P.X.H., C.Y.L. and L.R. analyzed the data. Z.W.C., C.C.H., R.W.S. and F.N. contributed the reagents and materials. All authors approved the manuscript.
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Goh, Y.S., Mao, H., Hor, P.X. et al. Vaccine-induced mouse antibodies targeting Plasmodium falciparum PfVFT antigen inhibit blood stages through multiple mechanisms. npj Vaccines (2026). https://doi.org/10.1038/s41541-026-01433-9
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DOI: https://doi.org/10.1038/s41541-026-01433-9
