Journal
CELL REPORTS
Volume 20, Issue 9, Pages 2251-2261Publisher
CELL PRESS
DOI: 10.1016/j.celrep.2017.08.023
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Funding
- German Center for Infection Research (DZIF)
- Universitatsklinikum Hamburg-Eppendorf
- Wellcome Trust
- German Ministry for Education and Research (BMBF) through the Ebokon program
- German Ministry of Health (BMG)
- DZIF through a MD/Ph.D. stipend
- DZIF through the Clinician Scientist Program of the Faculty of Medicine, University Medical Center Hamburg-Eppendorf (Hamburg, Germany)
- EU-IMI-2
- NIH
- INSERM
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Predicting vaccine efficacy remains a challenge. We used a systems vaccinology approach to identify early innate immune correlates of antibody induction in humans receiving the Ebola vaccine rVSV-ZEBOV. Blood samples from days 0, 1, 3, 7, and 14 were analyzed for changes in cytokine levels, innate immune cell subsets, and gene expression. Integrative statistical analyses with cross-validation identified a signature of 5 early innate markers correlating with antibody titers on day 28 and beyond. Among those, IP-10 on day 3 and MFI of CXCR6 on NK cells on day 1 were independent correlates. Consistently, we found an early gene expression signature linked to IP-10. This comprehensive characterization of early innate immune responses to the rVSV-ZEBOV vaccine in humans revealed immune signatures linked to IP-10. These results suggest correlates of vaccine- induced antibody induction and provide a rationale to explore strategies for augmenting the effectiveness of vaccines through manipulation of IP-10.
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