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The Human Immune Response to Dengue Virus Is Dominated by Highly Cross-Reactive Antibodies Endowed with Neutralizing and Enhancing Activity
Open accessAbstract
Summary Antibodies protect against homologous Dengue virus (DENV) infection but can precipitate severe dengue by promoting heterotypic virus entry via Fcγ receptors (FcγR). We immortalized memory B cells from individuals after primary or secondary infection and analyzed anti-DENV monoclonal antibodies (mAbs) thus generated. MAbs to envelope (E) protein domain III (DIII) were either serotype specific or cross-reactive and potently neutralized DENV infection. DI/DII- or viral membrane protein prM-reactive mAbs neutralized poorly and showed broad cross-reactivity with the four DENV serotypes. All mAbs enhanced infection at subneutralizing concentrations. Three mAbs targeting distinct epitopes on the four DENV serotypes and engineered to prevent FcγR binding did not enhance infection and neutralized DENV in vitro and in vivo as postexposure therapy in a mouse model of lethal DENV infection. Our findings reveal an unexpected degree of cross-reactivity in human antibodies against DENV and illustrate the potential for an antibody-based therapy to control severe dengue.
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Traggiai, E., Becker, S., Subbarao, K., Kolesnikova, L., Uematsu, Y., Gismondo, M. R., Murphy, B. R., Rappuoli, R., & Lanzavecchia, A. (2004) · Nature Medicine · doi:10.1038/nm1080 · Cited by 697
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Richner, J. M., Himansu, S., Dowd, K. A., Butler, S. L., Salazar, V., Fox, J. M., Julander, J. G., Tang, W. W., Shresta, S., Pierson, T. C., et al. (2017) · Cell · doi:10.1016/j.cell.2017.02.017 · Cited by 909
Self-citationThe promise and challenge of high-throughput sequencing of the antibody repertoire
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Human antibody responses after dengue virus infection are highly cross-reactive to Zika virus
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Structural basis of potent Zika–dengue virus antibody cross-neutralization
Barba-Spaeth, G., Dejnirattisai, W., Rouvinski, A., Vaney, M.-C., Medits, I., Sharma, A., Simon-Lorière, E., Sakuntabhai, A., Cao-Lormeau, V.-M., Haouz, A., et al. (2016) · Nature · doi:10.1038/nature18938 · Cited by 533
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Metadata
- Authors
- Beltramello, M., Williams, K. L., Simmons, C. P., Macagno, A., Simonelli, L., Quyen, N. T. H., Sukupolvi-Petty, S., Navarro-Sanchez, E., Young, P. R., de Silva, A. M., Rey, F. A., Varani, L., Whitehead, S. S., Diamond, M. S., Harris, E., Lanzavecchia, A., & Sallusto, F.
- Venue
- Cell Host & Microbe
- Publisher
- Elsevier BV
- Published
- 2010-09
- Volume
- 8
- Issue
- 3
- Pages
- 271-283
- ISSN
- 1931-3128 (ISSN-L)
- OpenAlex
- W2051298245
- Cited by
- 592
- References
- 1
- FWCI
- 33.40
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Beltramello, M., Williams, K. L., Simmons, C. P., Macagno, A., Simonelli, L., Quyen, N. T. H., Sukupolvi-Petty, S., Navarro-Sanchez, E., Young, P. R., de Silva, A. M., Rey, F. A., Varani, L., Whitehead, S. S., Diamond, M. S., Harris, E., Lanzavecchia, A., & Sallusto, F. (2010). The Human Immune Response to Dengue Virus Is Dominated by Highly Cross-Reactive Antibodies Endowed with Neutralizing and Enhancing Activity. Cell Host & Microbe. https://doi.org/10.1016/j.chom.2010.08.007
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Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
