ArticleCell reports2023
Cytotoxicity of human antibodies targeting the circumsporozoite protein is amplified by 3D substrate and correlates with protection.
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 14 papers.
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Who cites it
14 citing papers in PubMed, 19 citations in OpenAlex.
- Malaria vaccine protection against intradermal or venous parasites: a randomized phase 2b human challenge trial.Nature medicine · 2026Trial
- A structure-based epitope tagging approach identifies vulnerable sites on the malarial P36-P52 protein complex for antibody-mediated neutralization of Plasmodium sporozoites.PLoS pathogens · 2026Article
- Relevance of the antibody Fc fragment and epitope valency in protection against malaria sporozoites.EMBO reports · 2026Article
- Influence of biophysical and biochemical cues on Plasmodium sporozoite dynamics in skin tissue.Parasites & vectors · 2025Review
- Comparison of major, minor and junctional circumsporozoite protein epitopes for malaria vaccine design.NPJ vaccines · 2025Article
- Analysis of Fc-dependent effector functions of anti-malaria circumsporozoite protein antibodies.Microbiology spectrum · 2025Article
- Elicitation of liver-stage immunity by nanoparticle immunogens displaying P. falciparum CSP-derived antigens.NPJ vaccines · 2025Article
- FcγR binding differentially contributes to protection by two human monoclonal antibodies targetingScience translational medicine · 2025Article
- Late killing ofeLife · 2025Article
- 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
- Article
- Killing ofMicroorganisms · 2024Article
- Molecular determinants of cross-reactivity and potency by VH3-33 antibodies against the Plasmodium falciparum circumsporozoite protein.Cell reports · 2023Article
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Authors and funding
19 authors at 4 institutions in 3 countries.
Funding
Abstract
Human monoclonal antibodies (hmAbs) targeting the Plasmodium falciparum circumsporozoite protein (PfCSP) on the sporozoite surface are a promising tool for preventing malaria infection. However, their mechanisms of protection remain unclear. Here, using 13 distinctive PfCSP hmAbs, we provide a comprehensive view of how PfCSP hmAbs neutralize sporozoites in host tissues. Sporozoites are most vulnerable to hmAb-mediated neutralization in the skin. However, rare but potent hmAbs additionally neutralize sporozoites in the blood and liver. Efficient protection in tissues mainly associates with high-affinity and high-cytotoxicity hmAbs inducing rapid parasite loss-of-fitness in the absence of complement and host cells in vitro. A 3D-substrate assay greatly enhances hmAb cytotoxicity and mimics the skin-dependent protection, indicating that the physical stress imposed on motile sporozoites by the skin is crucial for unfolding the protective potential of hmAbs. This functional 3D cytotoxicity assay can thus be useful for downselecting potent anti-PfCSP hmAbs and vaccines.
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