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PLoS One. 2012;7(4):e33451. doi: 10.1371/journal.pone.0033451. Epub 2012 Apr 3.

A human PrM antibody that recognizes a novel cryptic epitope on dengue E glycoprotein.

Author information

1
Bio-Defence Programme, DMERI, DSO National Laboratories, Singapore, Singapore.

Abstract

Dengue virus (DENV) is a major mosquito-borne pathogen infecting up to 100 million people each year; so far no effective treatment or vaccines are available. Recently, highly cross-reactive and infection-enhancing pre-membrane (prM)-specific antibodies were found to dominate the anti-DENV immune response in humans, raising concern over vaccine candidates that contain native dengue prM sequences. In this study, we have isolated a broadly cross-reactive prM-specific antibody, D29, during a screen with a non-immunized human Fab-phage library against the four serotypes of DENV. The antibody is capable of restoring the infectivity of virtually non-infectious immature DENV (imDENV) in FcγR-bearing K562 cells. Remarkably, D29 also cross-reacted with a cryptic epitope on the envelope (E) protein located to the DI/DII junction as evidenced by site-directed mutagenesis. This cryptic epitope, while inaccessible to antibody binding in a native virus particle, may become exposed if E is not properly folded. These findings suggest that generation of anti-prM antibodies that enhance DENV infection may not be completely avoided even with immunization strategies employing E protein alone or subunits of E proteins.

PMID:
22509258
PMCID:
PMC3317930
DOI:
10.1371/journal.pone.0033451
[Indexed for MEDLINE]
Free PMC Article

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