Early Transcriptional Responses After Dengue Vaccination Mirror the Response to Natural Infection and Predict Neutralizing Antibody Titers. (14th July 2018)

• Record Type: Journal Article
• Authors: Popper, Stephen J; Strouts, Fiona R; Lindow, Janet C; Cheng, Henry K; Montoya, Magelda; Balmaseda, Angel; Durbin, Anna P; Whitehead, Stephen S; Harris, Eva; Kirkpatrick, Beth D; Relman, David A
• Is Part Of: Journal of infectious diseases. Volume 218:Number 12(2018)
• Page Start: 1911
• Page End: 1921
• Publication Date: 2018-07-14
• Subjects: dengue -- vaccine -- gene expression -- correlates of protection -- neutralizing antibody; Communicable diseases -- Periodicals; Diseases -- Causes and theories of causation -- Periodicals; Medicine -- Periodicals; Communicable Diseases -- Periodicals; Electronic journals; 616.9
• DOI: 10.1093/infdis/jiy434
• Languages: English
• ISSNs: 0022-1899

Abstract

Abstract : Interferon- and cell cycle–associated gene transcript abundance levels in the peripheral blood of dengue vaccine recipients on days 8 and 9 postvaccination were associated with dengue neutralizing antibody titers on day 42, and mirrored responses in primary dengue infection, suggesting the possibility of predicting protective immunity. 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. Clinical Trials Registration: NCT00831012.