ABSTRACT
Background Several promising live attenuated virus (LAV) dengue vaccines are in development, but information about innate immune responses and early correlates of protection are 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 NIH 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 versus 21 post-vaccination; 3,210 versus 286 transcripts with significant fold-change), but shared gene modules were induced in the same sequence. The abundance of 131 transcripts on days 8 and 9 post-vaccination was strongly correlated with NAb titers measured 6 weeks post-vaccination.
Conclusions LAV dengue vaccination elicits early transcriptional responses that mirror those found in symptomatic natural infection and provide candidate early markers of protection against DENV infection.
Clinical Trial Registration Number: NCT00831012 (available at clinicaltrials.gov)
Footnotes
Financial Support. This work was supported by the National Institute of Allergy and Infectious Diseases Division of Intramural Research and Division of Microbiology and Infectious Diseases (U19 AI109761, D.A.R.; U54 AI065359, A.B.), by the Thomas C. and Joan M. Merigan Endowment at Stanford University (D.A.R.), and by a grant (VE-1) from the Pediatric Dengue Vaccine Initiative of the Bill and Melinda Gates Foundation (E.H.).
Conflict of Interest. All authors: No reported conflicts of interest.