Identification of a novel infection-enhancing epitope on dengue prM using a dengue cross-reacting monoclonal antibody.
BMC Microbiol
; 13: 194, 2013 Aug 29.
Article
en En
| MEDLINE
| ID: mdl-23987307
ABSTRACT
BACKGROUND:
Dengue virus (DENV) infection is the most important arthropod- borne viral disease in human, but antiviral therapy and approved vaccines remain unavailable due to antibody-dependent enhancement (ADE) phenomenon. Many studies showed that pre-membrane (prM)-specific antibodies do not efficiently neutralize DENV infection but potently promote ADE infection. However, most of the binding epitopes of these antibodies remain unknown.RESULTS:
In the present study, we characterized a DENV cross-reactive monoclonal antibody (mAb), 4D10, that neutralized poorly but potently enhanced infection of four standard DENV serotypes and immature DENV (imDENV) over a broad range of concentration. In addition, the epitope of 4D10 was successfully mapped to amino acid residues 14 to18 of DENV1-4 prM protein using a phage-displayed peptide library and comprehensive bioinformatics analysis. We found that the epitope was DENV serocomplex cross-reactive and showed to be highly immunogenic in Balb/c mice. Furthermore, antibody against epitope peptide PL10, like 4D10, showed broad cross-reactivity and weak neutralizing activtity with four standard DENV serotypes and imDENV but significantly promoted ADE infection. These results suggested 4D10 and anti-PL10 sera were infection-enhancing antibodies and PL10 was infection-enhancing epitope.CONCLUSIONS:
We mapped the epitope of 4D10 to amino acid residues 14 to18 of DENV1-4 prM and found that this epitope was infection-enhancing. These findings may provide significant implications for future vaccine design and facilitate understanding the pathogenesis of DENV infection.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Proteínas del Envoltorio Viral
/
Anticuerpos Bloqueadores
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Virus del Dengue
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Anticuerpos Monoclonales
/
Anticuerpos Antivirales
/
Epítopos
/
Antígenos Virales
Tipo de estudio:
Diagnostic_studies
/
Prognostic_studies
Límite:
Adult
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Animals
/
Female
/
Humans
Idioma:
En
Revista:
BMC Microbiol
Asunto de la revista:
MICROBIOLOGIA
Año:
2013
Tipo del documento:
Article
País de afiliación:
China