Structural and mechanistic basis of neutralization by a pan-hantavirus protective antibody.
Sci Transl Med
; 15(700): eadg1855, 2023 06 14.
Article
em En
| MEDLINE
| ID: mdl-37315110
ABSTRACT
Emerging rodent-borne hantaviruses cause severe diseases in humans with no approved vaccines or therapeutics. We recently isolated a monoclonal broadly neutralizing antibody (nAb) from a Puumala virus-experienced human donor. Here, we report its structure bound to its target, the Gn/Gc glycoprotein heterodimer comprising the viral fusion complex. The structure explains the broad activity of the nAb It recognizes conserved Gc fusion loop sequences and the main chain of variable Gn sequences, thereby straddling the Gn/Gc heterodimer and locking it in its prefusion conformation. We show that the nAb's accelerated dissociation from the divergent Andes virus Gn/Gc at endosomal acidic pH limits its potency against this highly lethal virus and correct this liability by engineering an optimized variant that sets a benchmark as a candidate pan-hantavirus therapeutic.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Orthohantavírus
/
Anticorpos Antivirais
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article