A human PrM antibody that recognizes a novel cryptic epitope on dengue E glycoprotein.
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 res...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2012-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3317930?pdf=render |
| _version_ | 1830518370823307264 |
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| author | Annie Hoi Yi Chan Hwee Cheng Tan Angelia Yee Chow Angeline Pei Chiew Lim Shee Mei Lok Nicole J Moreland Subhash G Vasudevan Paul A MacAry Eng Eong Ooi Brendon J Hanson |
| author_facet | Annie Hoi Yi Chan Hwee Cheng Tan Angelia Yee Chow Angeline Pei Chiew Lim Shee Mei Lok Nicole J Moreland Subhash G Vasudevan Paul A MacAry Eng Eong Ooi Brendon J Hanson |
| author_sort | Annie Hoi Yi Chan |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-22T04:17:28Z |
| format | Article |
| id | doaj.art-7adfda388ba34620a6adc94b80ebbc04 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-22T04:17:28Z |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
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| series | PLoS ONE |
| spelling | doaj.art-7adfda388ba34620a6adc94b80ebbc042022-12-21T18:39:22ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0174e3345110.1371/journal.pone.0033451A human PrM antibody that recognizes a novel cryptic epitope on dengue E glycoprotein.Annie Hoi Yi ChanHwee Cheng TanAngelia Yee ChowAngeline Pei Chiew LimShee Mei LokNicole J MorelandSubhash G VasudevanPaul A MacAryEng Eong OoiBrendon J HansonDengue 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.http://europepmc.org/articles/PMC3317930?pdf=render |
| spellingShingle | Annie Hoi Yi Chan Hwee Cheng Tan Angelia Yee Chow Angeline Pei Chiew Lim Shee Mei Lok Nicole J Moreland Subhash G Vasudevan Paul A MacAry Eng Eong Ooi Brendon J Hanson A human PrM antibody that recognizes a novel cryptic epitope on dengue E glycoprotein. PLoS ONE |
| title | A human PrM antibody that recognizes a novel cryptic epitope on dengue E glycoprotein. |
| title_full | A human PrM antibody that recognizes a novel cryptic epitope on dengue E glycoprotein. |
| title_fullStr | A human PrM antibody that recognizes a novel cryptic epitope on dengue E glycoprotein. |
| title_full_unstemmed | A human PrM antibody that recognizes a novel cryptic epitope on dengue E glycoprotein. |
| title_short | A human PrM antibody that recognizes a novel cryptic epitope on dengue E glycoprotein. |
| title_sort | human prm antibody that recognizes a novel cryptic epitope on dengue e glycoprotein |
| url | http://europepmc.org/articles/PMC3317930?pdf=render |
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