Cytotoxicity of human antibodies targeting the circumsporozoite protein is amplified by 3D substrate and correlates with protection.
Cell Rep
; 42(7): 112681, 2023 07 25.
Article
en En
| MEDLINE
| ID: mdl-37389992
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.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Malaria Falciparum
/
Vacunas contra la Malaria
/
Malaria
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Cell Rep
Año:
2023
Tipo del documento:
Article
País de afiliación:
Francia