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

Stephen J. Popper, Fiona R. Strouts, Janet C. Lindow, Henry K. Cheng, Magelda Montoya, Angel Balmaseda, Anna P Durbin, Stephen S. Whitehead, Eva Harris, Beth D. Kirkpatrick, David A. Relman

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)1911-1921
Number of pages11
JournalThe Journal of infectious diseases
Volume218
Issue number12
DOIs
StatePublished - Nov 5 2018

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Dengue
Dengue Vaccines
Neutralizing Antibodies
Dengue Virus
Vaccination
Infection
Viral Structures
Attenuated Vaccines
Hospitalized Child
Gene Regulatory Networks
National Institutes of Health (U.S.)
Human Genome
Virus Diseases
Innate Immunity
Interferons
Volunteers
Immunization
Cell Cycle
Clinical Trials
Gene Expression

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

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

In: The Journal of infectious diseases, Vol. 218, No. 12, 05.11.2018, p. 1911-1921.

Research output: Contribution to journalArticle

Popper, SJ, Strouts, FR, Lindow, JC, Cheng, HK, Montoya, M, Balmaseda, A, Durbin, AP, Whitehead, SS, Harris, E, Kirkpatrick, BD & Relman, DA 2018, 'Early Transcriptional Responses After Dengue Vaccination Mirror the Response to Natural Infection and Predict Neutralizing Antibody Titers', The Journal of infectious diseases, vol. 218, no. 12, pp. 1911-1921. https://doi.org/10.1093/infdis/jiy434
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. / Early Transcriptional Responses After Dengue Vaccination Mirror the Response to Natural Infection and Predict Neutralizing Antibody Titers. In: The Journal of infectious diseases. 2018 ; Vol. 218, No. 12. pp. 1911-1921.
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