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5 results on '"Huntwork, Richard H.C."'

1. Molecular determinants of cross-reactivity and potency by VH3-33 antibodies against the Plasmodium falciparum circumsporozoite protein

Author

Thai, Elaine, Murugan, Rajagopal, Binter, Špela, Burn Aschner, Clare, Prieto, Katherine, Kassardjian, Audrey, Obraztsova, Anna S., Kang, Ryu Won, Flores-Garcia, Yevel, Mathis-Torres, Shamika, Li, Kan, Horn, Gillian Q., Huntwork, Richard H.C., Bolscher, Judith M., de Bruijni, Marloes H.C., Sauerwein, Robert, Dennison, S. Moses, Tomaras, Georgia D., Zavala, Fidel, Kellam, Paul, Wardemann, Hedda, and Julien, Jean-Philippe

Published
2023
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2. SARS-CoV-2 antibodies specific to the mesa and inner side of spike protein receptor binding domain maintain high affinities for both D614G and b.1.351 variants

Author

Li, Kan, primary, Huntwork, Richard H.C., additional, Horn, Gillian Q., additional, Feeney, Elizabeth, additional, Hastie, Kathryn M., additional, Li, Haoyang, additional, Rayaprolu, Vamseedhar, additional, Olmedillas, Olmedillas, additional, Schendel, Sharon L., additional, Heise, Mark, additional, Baric, Ralph S., additional, Alam, S. Munir, additional, Ollmann Saphire, Erica, additional, Tomaras, Georgia D., additional, and Dennison, S. Moses, additional

Published
2022
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5. Molecular determinants of cross-reactivity and potency by VH3-33 antibodies against the Plasmodium falciparumcircumsporozoite protein

Author

Thai, Elaine, Murugan, Rajagopal, Binter, Špela, Burn Aschner, Clare, Prieto, Katherine, Kassardjian, Audrey, Obraztsova, Anna S., Kang, Ryu Won, Flores-Garcia, Yevel, Mathis-Torres, Shamika, Li, Kan, Horn, Gillian Q., Huntwork, Richard H.C., Bolscher, Judith M., de Bruijni, Marloes H.C., Sauerwein, Robert, Dennison, S. Moses, Tomaras, Georgia D., Zavala, Fidel, Kellam, Paul, Wardemann, Hedda, and Julien, Jean-Philippe

Abstract

IGHV3-33-encoded antibodies are prevalent in the human humoral response against the Plasmodium falciparumcircumsporozoite protein (PfCSP). Among VH3-33 antibodies, cross-reactivity between PfCSP major repeat (NANP), minor (NVDP), and junctional (NPDP) motifs is associated with high affinity and potent parasite inhibition. However, the molecular basis of antibody cross-reactivity and the relationship with efficacy remain unresolved. Here, we perform an extensive structure-function characterization of 12 VH3-33 anti-PfCSP monoclonal antibodies (mAbs) with varying degrees of cross-reactivity induced by immunization of mice expressing a human immunoglobulin gene repertoire. We identify residues in the antibody paratope that mediate cross-reactive binding and delineate four distinct epitope conformations induced by antibody binding, with one consistently associated with high protective efficacy and another that confers comparably potent inhibition of parasite liver invasion. Our data show a link between molecular features of cross-reactive VH3-33 mAb binding to PfCSP and mAb potency, relevant for the development of antibody-based interventions against malaria.

Published
2023
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