ArticleCell reports2023
Molecular determinants of cross-reactivity and potency by VH3-33 antibodies against the Plasmodium falciparum circumsporozoite protein.
Article in Cell reports, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 19 citations in OpenAlex.
- Duration and association with protection of NANP-repeat-specific and C-terminus-specific anti-circumsporozoite protein IgG responses following RTS,S/AS01The Lancet. Infectious diseases · 2026Trial
- CRISPR-mediated precise large fragment insertion in zygotes enables rapid generation of humanized immunoglobulin heavy-chain mice.Immunity · 2026Article
- Structural basis for conserved and distinct antigen recognition by a lineage of malaria-protective antibodies.PLoS pathogens · 2026Article
- Protective immunity against malaria by a nanoparticle CIS43-based junctional vaccine alone or in combination with R21.NPJ vaccines · 2026Article
- Machine learning enables de novo multiepitope design ofProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Comparison of major, minor and junctional circumsporozoite protein epitopes for malaria vaccine design.NPJ vaccines · 2025Article
- Protective immunity against malaria by a nanoparticle CIS43-based junctional vaccine alone or in combination with R21.bioRxiv : the preprint server for biology · 2025Article
- Article
- Elicitation of liver-stage immunity by nanoparticle immunogens displaying P. falciparum CSP-derived antigens.NPJ vaccines · 2025Article
- Targeting Bottlenecks in Malaria Transmission: Antibody-Epitope Descriptions Guide the Design of Next-Generation Biomedical Interventions.Immunological reviews · 2025Review
- Article
- Protective antibodies target cryptic epitope unmasked by cleavage of malaria sporozoite protein.Science (New York, N.Y.) · 2025Article
- Monoclonal antibodies to the circumsporozoite proteins as an emerging tool for malaria prevention.Nature immunology · 2024Review
Corrections and comments
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Authors and funding
22 authors at 8 institutions in 5 countries.
Funding
Abstract
IGHV3-33-encoded antibodies are prevalent in the human humoral response against the Plasmodium falciparum circumsporozoite 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.
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