3 years ago

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

Systems Vaccinology Identifies an Early Innate Immune Signature as a Correlate of Antibody Responses to the Ebola Vaccine rVSV-ZEBOV
Verena Krähling, Madeleine Zinser, Rodolphe Thiébaut, Ansgar Lohse, Markus Eickmann, Gloria Martrus, Stephan Becker, Rahel Kasonta, Laura Richert, Urte Matschl, Hans Stubbe, VEBCON Consortium, Hadrien Lorenzo, Anne Rechtien, Marylyn Addo, Marcus Altfeld, Christine Dahlke, Boris Hejblum

Summary

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.

Publisher URL: http://www.cell.com/cell-reports/fulltext/S2211-1247(17)31115-4

DOI: 10.1016/j.celrep.2017.08.023

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