Protective antibodies target cryptic epitope unmasked by cleavage of malaria sporozoite protein

The most advanced monoclonal antibodies (mAbs) and vaccines against malaria target the central repeat region or closely related sequences within the Plasmodium falciparum circumsporozoite protein (PfCSP). Here, using an antigen-agnostic strategy to interrogate human antibody responses to whole sporozoites, we identify a class of mAbs that target a cryptic PfCSP epitope that is only exposed after cleavage and subsequent pyroglutamylation (pGlu) of the newly formed N-terminus. This pGlu-CSP epitope is not targeted by current anti-PfCSP mAbs and is not included in the licensed malaria vaccines. MAD21-101, the most potent mAb in this class, confers sterile protection against Pf infection in a human liver-chimeric mouse model. These findings reveal a site of vulnerability on the sporozoite surface that can be targeted by next-generation antimalarial interventions., , , # Protective antibodies target cryptic epitope unmasked by cleavage of malaria sporozoite protein

[https://doi.org/10.5061/dryad.fttdz0930](https://doi.org/10.5061/dryad.fttdz0930)

## Description of the data and file structure

\# Dataset: Protective antibodies target cryptic epitope unmasked by cleavage of malaria sporozoite protein

\[Access this dataset on Dryad]( [[https://doi.org/10.5061/dryad.fttdz0930](https://doi.org/10.5061/dryad.fttdz0930))

\#Dataset file formats:

We have submitted our raw dataset on the characterization of the monoclonal antibodies in an Excel file (‘Dryad_dataset_adr0510_Science.xlsx’). Each sheet within the Excel file is labelled with a unique figure number and contains the data relevant to the figure by which it is labelled. Within each sheet, datapoints are entered under the relevant sub-figure number. We have also submitted the isothermal titration calorimetry (ITC) dataset as a compressed zip folder (‘ITC_fig._S8A_raw_data.zip’). Each .itc file with...