Open AccessA Human PrM Antibody That Recognizes a Novel Cryptic Epitope on Dengue E Glycoprotein
Author(s) -
Annie Hoi Yi Chan,
Hwee Cheng Tan,
Angelia Chow,
Angeline Lim,
Shee-Mei Lok,
Nicole J. Moreland,
Subhash G. Vasudevan,
Paul A. MacAry,
Eng Eong Ooi,
Brendon J. Hanson
Publication year - 2012
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0033451
Subject(s) - epitope , dengue virus , virology , biology , dengue vaccine , antibody , dengue fever , infectivity , antibody dependent enhancement , virus , immunology
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.