Author
Listed:
- Alexander Rouvinski
(Institut Pasteur, Unité de Virologie Structurale
CNRS UMR 3569 Virologie
Present address: Department of Microbiology and Molecular Genetics, Kuvin Center for the Study of Infectious and Tropical Diseases, Institute for Medical Research Israel-Canada, The Hebrew University-Hadassah Medical School, The Hebrew University of Jerusalem, Jerusalem, Israel)
- Wanwisa Dejnirattisai
(Hammersmith Hospital Campus, Imperial College London)
- Pablo Guardado-Calvo
(Institut Pasteur, Unité de Virologie Structurale
CNRS UMR 3569 Virologie)
- Marie-Christine Vaney
(Institut Pasteur, Unité de Virologie Structurale
CNRS UMR 3569 Virologie)
- Arvind Sharma
(Institut Pasteur, Unité de Virologie Structurale
CNRS UMR 3569 Virologie)
- Stéphane Duquerroy
(Institut Pasteur, Unité de Virologie Structurale
CNRS UMR 3569 Virologie
Université Paris-Sud, Faculté des Sciences)
- Piyada Supasa
(Hammersmith Hospital Campus, Imperial College London)
- Wiyada Wongwiwat
(Hammersmith Hospital Campus, Imperial College London)
- Ahmed Haouz
(Institut Pasteur, Protéopôle, CNRS UMR 3528)
- Giovanna Barba-Spaeth
(Institut Pasteur, Unité de Virologie Structurale
CNRS UMR 3569 Virologie)
- Juthathip Mongkolsapaya
(Hammersmith Hospital Campus, Imperial College London
Dengue Haemorrhagic Fever Research Unit, Office for Research and Development, Faculty of Medicine, Siriraj Hospital, Mahidol University)
- Félix A. Rey
(Institut Pasteur, Unité de Virologie Structurale
CNRS UMR 3569 Virologie)
- Gavin R. Screaton
(Hammersmith Hospital Campus, Imperial College London)
Abstract
A problem in the search for an efficient vaccine against dengue virus is the immunodominance of the fusion loop epitope (FLE), a segment of the envelope protein E that is buried at the interface of the E dimers coating mature viral particles. Anti-FLE antibodies are broadly cross-reactive but poorly neutralizing, displaying a strong infection enhancing potential. FLE exposure takes place via dynamic ‘breathing’ of E dimers at the virion surface. In contrast, antibodies targeting the E dimer epitope (EDE), readily exposed at the E dimer interface over the region of the conserved fusion loop, are very potent and broadly neutralizing. We here engineer E dimers locked by inter-subunit disulfide bonds, and show by X-ray crystallography and by binding to a panel of human antibodies that these engineered dimers do not expose the FLE, while retaining the EDE exposure. These locked dimers are strong immunogen candidates for a next-generation vaccine.
Suggested Citation
Alexander Rouvinski & Wanwisa Dejnirattisai & Pablo Guardado-Calvo & Marie-Christine Vaney & Arvind Sharma & Stéphane Duquerroy & Piyada Supasa & Wiyada Wongwiwat & Ahmed Haouz & Giovanna Barba-Spaeth, 2017.
"Covalently linked dengue virus envelope glycoprotein dimers reduce exposure of the immunodominant fusion loop epitope,"
Nature Communications, Nature, vol. 8(1), pages 1-12, August.
Handle:
RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms15411
DOI: 10.1038/ncomms15411
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