The human immune response to Dengue virus is dominated by highly cross-reactive antibodies endowed with neutralizing and enhancing activity

Beltramello, Martina, Williams, Katherine L., Simmons, Cameron P., Macagno, Annalisa, Simonelli, Luca, Quyen, Nguyen Than Ha, Sukupolvi-Petty, Solia, Navarro-Sanchez, Erika, Young, Paul R., de Silva, Aravinda M., Rey, Felix A., Varani, Luca, Whitehead, Stephen S., Diamond, Michael S., Harris, Eva, Lanzavecchia, Antonio and Sallusto, Federica (2010) The human immune response to Dengue virus is dominated by highly cross-reactive antibodies endowed with neutralizing and enhancing activity. Cell Host and Microbe, 8 3: 271-283. doi:10.1016/j.chom.2010.08.007


Author Beltramello, Martina
Williams, Katherine L.
Simmons, Cameron P.
Macagno, Annalisa
Simonelli, Luca
Quyen, Nguyen Than Ha
Sukupolvi-Petty, Solia
Navarro-Sanchez, Erika
Young, Paul R.
de Silva, Aravinda M.
Rey, Felix A.
Varani, Luca
Whitehead, Stephen S.
Diamond, Michael S.
Harris, Eva
Lanzavecchia, Antonio
Sallusto, Federica
Title The human immune response to Dengue virus is dominated by highly cross-reactive antibodies endowed with neutralizing and enhancing activity
Journal name Cell Host and Microbe   Check publisher's open access policy
ISSN 1931-3128
1934-6069
Publication date 2010-09-16
Year available 2010
Sub-type Article (original research)
DOI 10.1016/j.chom.2010.08.007
Open Access Status Not yet assessed
Volume 8
Issue 3
Start page 271
End page 283
Total pages 13
Place of publication Cambridge, MA, United States
Publisher Cell Press
Language eng
Abstract 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.
Keyword Microbiology
Parasitology
Virology
Microbiology
Parasitology
Virology
MICROBIOLOGY
PARASITOLOGY
VIROLOGY
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID 126027
CRA14
R01-AI077955
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: ERA 2012 Admin Only
School of Chemistry and Molecular Biosciences
 
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Created: Thu, 20 Oct 2011, 19:47:19 EST by Paul Young on behalf of School of Chemistry & Molecular Biosciences