| Autor: |
Manuela C. Aguirre-Botero, Lawrence T. Wang, Pauline Formaglio, Eduardo Aliprandini, Jean-Michel Thiberge, Arne Schön, Yevel Flores-Garcia, Shamika Mathis-Torres, Barbara J. Flynn, Lais da Silva Pereira, Yann Le Duff, Mathew Hurley, Adéla Nacer, Paul W. Bowyer, Fidel Zavala, Azza H. Idris, Joseph R. Francica, Robert A. Seder, Rogerio Amino |
| Jazyk: |
angličtina |
| Rok vydání: |
2023 |
| Předmět: |
|
| Zdroj: |
Cell Reports, Vol 42, Iss 7, Pp 112681- (2023) |
| Druh dokumentu: |
article |
| ISSN: |
2211-1247 |
| DOI: |
10.1016/j.celrep.2023.112681 |
| Popis: |
Summary: 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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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