A "Trojan horse" bispecific-antibody strategy for broad protection against ebolaviruses.
Science
; 354(6310): 350-354, 2016 10 21.
Article
em En
| MEDLINE
| ID: mdl-27608667
ABSTRACT
There is an urgent need for monoclonal antibody (mAb) therapies that broadly protect against Ebola virus and other filoviruses. The conserved, essential interaction between the filovirus glycoprotein, GP, and its entry receptor Niemann-Pick C1 (NPC1) provides an attractive target for such mAbs but is shielded by multiple mechanisms, including physical sequestration in late endosomes. Here, we describe a bispecific-antibody strategy to target this interaction, in which mAbs specific for NPC1 or the GP receptor-binding site are coupled to a mAb against a conserved, surface-exposed GP epitope. Bispecific antibodies, but not parent mAbs, neutralized all known ebolaviruses by coopting viral particles themselves for endosomal delivery and conferred postexposure protection against multiple ebolaviruses in mice. Such "Trojan horse" bispecific antibodies have potential as broad antifilovirus immunotherapeutics.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Receptores Virais
/
Glicoproteínas de Membrana
/
Proteínas de Transporte
/
Proteínas do Envelope Viral
/
Anticorpos Biespecíficos
/
Doença pelo Vírus Ebola
/
Ebolavirus
/
Anticorpos Neutralizantes
/
Anticorpos Antivirais
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article