The light chain of the L9 antibody is critical for binding circumsporozoite protein minor repeats and preventing malaria.
Cell Rep
; 38(7): 110367, 2022 02 15.
Article
em En
| MEDLINE
| ID: mdl-35172158
ABSTRACT
L9 is a potent human monoclonal antibody (mAb) that preferentially binds two adjacent NVDP minor repeats and cross-reacts with NANP major repeats of the Plasmodium falciparum circumsporozoite protein (PfCSP) on malaria-infective sporozoites. Understanding this mAb's ontogeny and mechanisms of binding PfCSP will facilitate vaccine development. Here, we isolate mAbs clonally related to L9 and show that this B cell lineage has baseline NVDP affinity and evolves to acquire NANP reactivity. Pairing the L9 kappa light chain (L9κ) with clonally related heavy chains results in chimeric mAbs that cross-link two NVDPs, cross-react with NANP, and more potently neutralize sporozoites in vivo compared with their original light chain. Structural analyses reveal that the chimeric mAbs bound minor repeats in a type-1 ß-turn seen in other repeat-specific antibodies. These data highlight the importance of L9κ in binding NVDP on PfCSP to neutralize sporozoites and suggest that PfCSP-based immunogens might be improved by presenting ≥2 NVDPs.
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MEDLINE
Assunto principal:
Proteínas de Protozoários
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Malária Falciparum
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Cadeias Leves de Imunoglobulina
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Sequências Repetitivas de Aminoácidos
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Anticorpos Monoclonais
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article