@article{b95e28f9dbbf4a8a82fd93dd7f3898eb,
title = "Early transcriptional responses after dengue vaccination mirror the response to natural infection and predict neutralizing antibody titers",
abstract = "Background. Several promising live attenuated dengue vaccines are in development, but information about innate immune responses and early correlates of protection is lacking. Methods. We characterized human genome-wide transcripts in whole blood from 10 volunteers at 11 time points after immunization with the dengue virus type 3 (DENV-3) component of the National Institutes of Health dengue vaccine candidate TV003 and from 30 hospitalized children with acute primary DENV-3 infection. We compared day-specific gene expression patterns with subsequent neutralizing antibody (NAb) titers. Results. The transcriptional response to vaccination was largely confined to days 5-20 and was dominated by an interferon-associated signature and a cell cycle signature that peaked on days 8 and 14, respectively. Changes in transcript abundance were much greater in magnitude and scope in symptomatic natural infection than following vaccination (maximum fold-change >200 vs 21 postvaccination; 3210 vs 286 transcripts with significant fold-change), but shared gene modules were induced in the same sequence. The abundances of 131 transcripts on days 8 and 9 postvaccination were strongly correlated with NAb titers measured 6 weeks postvaccination. Conclusions. Live attenuated dengue vaccination elicits early transcriptional responses that mirror those found in symptomatic natural infection and provide candidate early markers of protection against DENV infection.",
keywords = "Correlates of protection, Dengue, Gene expression, Neutralizing antibody, Vaccine",
author = "Popper, {Stephen J.} and Strouts, {Fiona R.} and Lindow, {Janet C.} and Cheng, {Henry K.} and Magelda Montoya and Angel Balmaseda and Durbin, {Anna P.} and Whitehead, {Stephen S.} and Eva Harris and Kirkpatrick, {Beth D.} and Relman, {David A.}",
note = "Funding Information: Financial support. This work was supported by the Division of Intramural Research and Division of Microbiology and Infectious Diseases of the National Institute of Allergy and Infectious Diseases (grant numbers U19 AI109761 to D. A. R. and U54 AI065359 to A. B.); the Thomas C. and Joan M. Merigan Endowment at Stanford University (to D. A. R.); the Chan Zuckerberg Biohub (to D. A. R.); and the Pediatric Dengue Vaccine Initiative of the Bill & Melinda Gates Foundation (grant number VE-1 to E. H.). Potential conflicts of interest. All authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed. Funding Information: This work was supported by the Division of Intramural Research and Division of Microbiology and Infectious Diseases of the National Institute of Allergy and Infectious Diseases (grant numbers U19 AI109761 to D. A. R. and U54 AI065359 to A. B.); the Thomas C. and Joan M. Merigan Endowment at Stanford University (to D. A. R.); the Chan Zuckerberg Biohub (to D. A. R.); and the Pediatric Dengue Vaccine Initiative of the Bill & Melinda Gates Foundation (grant number VE-1 to E. H.). Publisher Copyright: {\textcopyright} 2018 Oxford University Press. All Rights Reserved.",
year = "2018",
month = nov,
day = "5",
doi = "10.1093/infdis/jiy434",
language = "English (US)",
volume = "218",
pages = "1911--1921",
journal = "Journal of Infectious Diseases",
issn = "0022-1899",
publisher = "Oxford University Press",
number = "12",
}