Development of a Potent and Protective Germline-Like Antibody Lineage Against Zika Virus in a Convalescent Human.
Front Immunol
; 10: 2424, 2019.
Article
en En
| MEDLINE
| ID: mdl-31708914
ABSTRACT
Zika virus (ZIKV) specific neutralizing antibodies hold great promise for antibody-based interventions and vaccine design against ZIKV infection. However, their development in infected patients remains unclear. Here, we applied next-generation sequencing (NGS) to probe the dynamic development of a potent and protective ZIKV E DIII-specific antibody ZK2B10 isolated from a ZIKV convalescent individual. The unbiased repertoire analysis showed dramatic changes in the usage of antibody variable region germline genes. However, lineage tracing of ZK2B10 revealed limited somatic hypermutation and transient expansion during the 12 months following the onset of symptoms. The NGS-derived, germline-like ZK2B10 somatic variants neutralized ZIKV potently and protected mice from lethal challenge of ZIKV without detectable cross-reactivity with Dengue virus (DENV). Site-directed mutagenesis identified two residues within the λ chain, N31 and S91, that are essential to the functional maturation of ZK2B10. The repertoire and lineage features unveiled here will help elucidate the developmental process and protective potential of E DIII-directed antibodies against ZIKV infection.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Interacciones Huésped-Patógeno
/
Virus Zika
/
Infección por el Virus Zika
/
Células Germinativas
/
Anticuerpos Antivirales
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Front Immunol
Año:
2019
Tipo del documento:
Article
País de afiliación:
China