Cooperativity mediated by rationally selected combinations of human monoclonal antibodies targeting the henipavirus receptor binding protein.
Cell Rep
; 36(9): 109628, 2021 08 31.
Article
en En
| MEDLINE
| ID: mdl-34469726
ABSTRACT
Hendra virus and Nipah virus (NiV), members of the Henipavirus (HNV) genus, are zoonotic paramyxoviruses known to cause severe disease across six mammalian orders, including humans. We isolated a panel of human monoclonal antibodies (mAbs) from the B cells of an individual with prior exposure to equine Hendra virus (HeV) vaccine, targeting distinct antigenic sites. The most potent class of cross-reactive antibodies achieves neutralization by blocking viral attachment to the host cell receptors ephrin-B2 and ephrin-B3, with a second class being enhanced by receptor binding. mAbs from both classes display synergistic activity in vitro. In a stringent hamster model of NiV Bangladesh (NiVB) infection, antibodies from both classes reduce morbidity and mortality and achieve synergistic protection in combination. These candidate mAbs might be suitable for use in a cocktail therapeutic approach to achieve synergistic potency and reduce the risk of virus escape.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Antivirales
/
Receptores Virales
/
Efrina-B2
/
Efrina-B3
/
Henipavirus
/
Infecciones por Henipavirus
/
Anticuerpos Neutralizantes
/
Anticuerpos Monoclonales
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Female
/
Humans
Idioma:
En
Año:
2021
Tipo del documento:
Article