Molecular characterization of a synthetic neutralizing antibody targeting p67 of Theileria parva
2025
Miersch, S. | Singer, A.U. | Chen, C. | Fellouse, F. | Gopalsamy, A. | Costa, L.S. e | Lacasta, Anna | Chege, Hannah | Chege, Naomi | Nene, Vishvanath | Sidhu, S.S.
The <i>Theileria parva</i> sporozoite surface antigen p67 is a target of the bovine humoral immune response that generates antibodies capable of providing protection against subsequent infection. As a result, p67 has been the subject of efforts aimed at the development of an anti-sporozoite subunit vaccine. Previous studies have identified neutralizing epitopes in the N- and C-terminal regions of the full-length protein and shown that immunization with a C-terminal fragment of p67 (p67C) alone is capable of eliciting protection. To identify additional neutralizing epitopes in p67C, selections were conducted against it using a phage-displayed synthetic antibody library. An antibody that neutralized the sporozoite in vitro was identified, and the crystal structure of a Fab:peptide complex was elucidated. Mutagenesis studies aimed at validating and further characterizing the Fab:peptide interaction identified critical residues involved in binding and neutralization. This study also validates distinct epitopes for previously reported neutralizing antibodies.
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