Potent human neutralizing antibodies against Nipah virus derived from two ancestral antibody heavy chains.
Nat Commun
; 15(1): 2987, 2024 Apr 06.
Article
in En
| MEDLINE
| ID: mdl-38582870
ABSTRACT
Nipah virus (NiV) is a World Health Organization priority pathogen and there are currently no approved drugs for clinical immunotherapy. Through the use of a naïve human phage-displayed Fab library, two neutralizing antibodies (NiV41 and NiV42) targeting the NiV receptor binding protein (RBP) were identified. Following affinity maturation, antibodies derived from NiV41 display cross-reactivity against both NiV and Hendra virus (HeV), whereas the antibody based on NiV42 is only specific to NiV. Results of immunogenetic analysis reveal a correlation between the maturation of antibodies and their antiviral activity. In vivo testing of NiV41 and its mature form (41-6) show protective efficacy against a lethal NiV challenge in hamsters. Furthermore, a 2.88 Å Cryo-EM structure of the tetrameric RBP and antibody complex demonstrates that 41-6 blocks the receptor binding interface. These findings can be beneficial for the development of antiviral drugs and the design of vaccines with broad spectrum against henipaviruses.
Full text:
1
Database:
MEDLINE
Main subject:
Nipah Virus
/
Henipavirus Infections
Limits:
Humans
Language:
En
Year:
2024
Type:
Article