Format

Send to

Choose Destination
Cell Rep. 2017 Aug 29;20(9):2251-2261. doi: 10.1016/j.celrep.2017.08.023.

Systems Vaccinology Identifies an Early Innate Immune Signature as a Correlate of Antibody Responses to the Ebola Vaccine rVSV-ZEBOV.

Author information

1
University Medical Center Hamburg-Eppendorf, 1(st) Department of Medicine, 20246 Hamburg, Germany; German Center for Infection Research (DZIF), Partner Site Hamburg-Lübeck-Borstel-Riems, 20246 Hamburg, Germany; Heinrich Pette Institute, Leibniz Institute for Experimental Virology, 20251 Hamburg, Germany. Electronic address: anne.rechtien@leibniz-hpi.de.
2
Heinrich Pette Institute, Leibniz Institute for Experimental Virology, 20251 Hamburg, Germany; INSERM U1219, INRIA SISTM, Bordeaux University, Bordeaux, France; Vaccine Research Institute, Creteil, France.
3
INSERM U1219, INRIA SISTM, Bordeaux University, Bordeaux, France; Vaccine Research Institute, Creteil, France.
4
Heinrich Pette Institute, Leibniz Institute for Experimental Virology, 20251 Hamburg, Germany.
5
University Medical Center Hamburg-Eppendorf, 1(st) Department of Medicine, 20246 Hamburg, Germany; German Center for Infection Research (DZIF), Partner Site Hamburg-Lübeck-Borstel-Riems, 20246 Hamburg, Germany.
6
University Medical Center Hamburg-Eppendorf, 1(st) Department of Medicine, 20246 Hamburg, Germany.
7
German Center for Infection Research (DZIF), Partner Site Hamburg-Lübeck-Borstel-Riems, 20246 Hamburg, Germany; Division of Infectious Diseases, Department of Medicine IV, LMU, 80336 Munich, Germany.
8
Philipps University Marburg, Institute for Virology, 35043 Marburg, Germany.
9
University Medical Center Hamburg-Eppendorf, 1(st) Department of Medicine, 20246 Hamburg, Germany; German Center for Infection Research (DZIF), Partner Site Hamburg-Lübeck-Borstel-Riems, 20246 Hamburg, Germany. Electronic address: ma.ddo@uke.de.

Abstract

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.

KEYWORDS:

Ebola vaccine; IP-10; RNA sequencing; emerging infections; innate immunity; rVSV-ZEBOV; systems vaccinology; viral immunity

PMID:
28854372
PMCID:
PMC5583508
DOI:
10.1016/j.celrep.2017.08.023
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center