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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. Clinical Trials Registration:NCT00831012.

SUBMITTER: Popper SJ

PROVIDER: S-EPMC6217718 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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Early Transcriptional Responses After Dengue Vaccination Mirror the Response to Natural Infection and Predict Neutralizing Antibody Titers.

Popper Stephen J SJ Strouts Fiona R FR Lindow Janet C JC Cheng Henry K HK Montoya Magelda M Balmaseda Angel A Durbin Anna P AP Whitehead Stephen S SS Harris Eva E Kirkpatrick Beth D BD Relman David A DA

The Journal of infectious diseases 20181101 12

<h4>Background</h4>Several promising live attenuated dengue vaccines are in development, but information about innate immune responses and early correlates of protection is lacking.<h4>Methods</h4>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 ...[more]

PMID: 30010906

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Early Transcriptional Responses After Dengue Vaccination Mirror the Response to Natural Infection and Predict Neutralizing Antibody Titers.

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Early Transcriptional Responses After Dengue Vaccination Mirror the Response to Natural Infection and Predict Neutralizing Antibody Titers.

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