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ResearchIn-Press PreviewImmunologyInfectious disease Open Access | 10.1172/jci.insight.198414

Epitope-specific competitive ELISA predicts malaria transmission-blocking vaccine Pfs230D1 activity measured in standard membrane feeding assay

Cristina A. Meehan,1 Matthew V. Cowles,1 Robert D. Morrison,1 Yuyan Yi,2 Jingwen Gu,2 Jen C.C. Hume,1 Mina P. Peyton,2 Issaka Sagara,3 Sara A. Healy,1 Jonathan P. Renn,1 and Patrick E. Duffy1

1Laboratory of Malaria Immunology and Vaccinology, Division of Intramural Re, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, United States of America

2Bioinformatics and Computational Biosciences Branch, Office of Cyber Infras, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, United States of America

3Malaria Research and Training Center, University of Sciences, Techniques and Technologies, Bamako, Mali

Find articles by Meehan, C. in: PubMed | Google Scholar

1Laboratory of Malaria Immunology and Vaccinology, Division of Intramural Re, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, United States of America

2Bioinformatics and Computational Biosciences Branch, Office of Cyber Infras, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, United States of America

3Malaria Research and Training Center, University of Sciences, Techniques and Technologies, Bamako, Mali

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1Laboratory of Malaria Immunology and Vaccinology, Division of Intramural Re, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, United States of America

2Bioinformatics and Computational Biosciences Branch, Office of Cyber Infras, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, United States of America

3Malaria Research and Training Center, University of Sciences, Techniques and Technologies, Bamako, Mali

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1Laboratory of Malaria Immunology and Vaccinology, Division of Intramural Re, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, United States of America

2Bioinformatics and Computational Biosciences Branch, Office of Cyber Infras, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, United States of America

3Malaria Research and Training Center, University of Sciences, Techniques and Technologies, Bamako, Mali

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1Laboratory of Malaria Immunology and Vaccinology, Division of Intramural Re, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, United States of America

2Bioinformatics and Computational Biosciences Branch, Office of Cyber Infras, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, United States of America

3Malaria Research and Training Center, University of Sciences, Techniques and Technologies, Bamako, Mali

Find articles by Gu, J. in: PubMed | Google Scholar |

1Laboratory of Malaria Immunology and Vaccinology, Division of Intramural Re, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, United States of America

2Bioinformatics and Computational Biosciences Branch, Office of Cyber Infras, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, United States of America

3Malaria Research and Training Center, University of Sciences, Techniques and Technologies, Bamako, Mali

Find articles by Hume, J. in: PubMed | Google Scholar

1Laboratory of Malaria Immunology and Vaccinology, Division of Intramural Re, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, United States of America

2Bioinformatics and Computational Biosciences Branch, Office of Cyber Infras, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, United States of America

3Malaria Research and Training Center, University of Sciences, Techniques and Technologies, Bamako, Mali

Find articles by Peyton, M. in: PubMed | Google Scholar

1Laboratory of Malaria Immunology and Vaccinology, Division of Intramural Re, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, United States of America

2Bioinformatics and Computational Biosciences Branch, Office of Cyber Infras, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, United States of America

3Malaria Research and Training Center, University of Sciences, Techniques and Technologies, Bamako, Mali

Find articles by Sagara, I. in: PubMed | Google Scholar |

1Laboratory of Malaria Immunology and Vaccinology, Division of Intramural Re, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, United States of America

2Bioinformatics and Computational Biosciences Branch, Office of Cyber Infras, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, United States of America

3Malaria Research and Training Center, University of Sciences, Techniques and Technologies, Bamako, Mali

Find articles by Healy, S. in: PubMed | Google Scholar |

1Laboratory of Malaria Immunology and Vaccinology, Division of Intramural Re, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, United States of America

2Bioinformatics and Computational Biosciences Branch, Office of Cyber Infras, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, United States of America

3Malaria Research and Training Center, University of Sciences, Techniques and Technologies, Bamako, Mali

Find articles by Renn, J. in: PubMed | Google Scholar

1Laboratory of Malaria Immunology and Vaccinology, Division of Intramural Re, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, United States of America

2Bioinformatics and Computational Biosciences Branch, Office of Cyber Infras, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, United States of America

3Malaria Research and Training Center, University of Sciences, Techniques and Technologies, Bamako, Mali

Find articles by Duffy, P. in: PubMed | Google Scholar |

Published January 1, 2026 - More info

JCI Insight. https://doi.org/10.1172/jci.insight.198414.
Copyright © 2026, Meehan et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Published January 1, 2026 - Version history
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Abstract

Functional antibody responses to malaria transmission-blocking vaccines (TBVs) are assessed using the Standard Membrane Feeding Assay (SMFA). This assay quantifies percentage reduction of oocyst levels in mosquitoes fed gametocytes mixed with antisera/antibodies, referred to as transmission-reducing activity (TRA). As TBVs advance to large clinical trials, new scalable assays are needed to characterize vaccine responses. Here, we developed an epitope-specific competitive ELISA platform (P230Compete) for TBV candidate Pfs230D1, based on single-chain variable fragments (scFv) against epitopes recognized by human monoclonal antibodies with high TRA. We quantified functional epitope-specific antibody responses (F) in Phase 1 Pfs230D1-EPA/AS01 vaccine trial participants, using 171 serum samples collected at two post-vaccination timepoints. Five antibody features were examined by P230Compete including total IgG (reported as ELISA units, EUF), IgG subclasses (IgG1F, IgG3F, IgG4F), and bound complement factor C1q (C1qF). EUF and IgG1F demonstrated strong correlation and excellent prediction of TRA≥80% in logistic regression analysis (AUC of 0.81 for both assays post-dose 3, and 0.80 and 0.76 post-dose 4). Furthermore, combining EUF and IgG1F showed even better predictive performance at each timepoint. P230Compete offers a promising proxy assay to replace SMFA in late-stage Pfs230D1 trials.

Supplemental material

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  • Version 1 (January 1, 2026): In-Press Preview
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