Back to Search
Start Over
Broadly neutralizing human antibodies against dengue virus identified by single B cell transcriptomics.
- Source :
-
ELife [Elife] 2019 Dec 10; Vol. 8. Date of Electronic Publication: 2019 Dec 10. - Publication Year :
- 2019
-
Abstract
- Eliciting broadly neutralizing antibodies (bNAbs) against the four dengue virus serotypes (DENV1-4) that are spreading into new territories is an important goal of vaccine design. To define bNAb targets, we characterized 28 antibodies belonging to expanded and hypermutated clonal families identified by transcriptomic analysis of single plasmablasts from DENV-infected individuals. Among these, we identified J9 and J8, two somatically related bNAbs that potently neutralized DENV1-4. Mutagenesis studies showed that the major recognition determinants of these bNAbs are in E protein domain I, distinct from the only known class of human bNAbs against DENV with a well-defined epitope. B cell repertoire analysis from acute-phase peripheral blood suggested that J9 and J8 followed divergent somatic hypermutation pathways, and that a limited number of mutations was sufficient for neutralizing activity. Our study suggests multiple B cell evolutionary pathways leading to DENV bNAbs targeting a new epitope that can be exploited for vaccine design.<br />Competing Interests: ND, AA, OS, EC, JP, MR, AS, LA, FR No competing interests declared, EW, DC, FZ, SE, SQ, KM, LG Inventor of the following patent application, which is co-owned by the Chan Zuckerberg Biohub and Stanford University: PCT patent application entitled ANTIBODIES AGAINST DENGUE VIRUS AND RELATED METHODS, Serial no. PCT/US2019/045427, filed August 7, 2019, MF, ED Employee of Integral Molecular, BD Employee and shareholder of Integral Molecular<br /> (© 2019, Durham et al.)
- Subjects :
- Antibodies, Neutralizing genetics
Antibodies, Viral genetics
DNA Mutational Analysis
Humans
Protein Binding
Viral Envelope Proteins metabolism
Antibodies, Neutralizing immunology
Antibodies, Viral immunology
B-Lymphocytes immunology
Dengue immunology
Dengue Virus immunology
Gene Expression Profiling
Subjects
Details
- Language :
- English
- ISSN :
- 2050-084X
- Volume :
- 8
- Database :
- MEDLINE
- Journal :
- ELife
- Publication Type :
- Academic Journal
- Accession number :
- 31820734
- Full Text :
- https://doi.org/10.7554/eLife.52384