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

Anne Rechtien; Laura Richert; Hadrien Lorenzo; Gloria Martrus; Boris Hejblum; Christine Dahlke; Rahel Kasonta; Madeleine Zinser; Hans Stubbe; Urte Matschl; Ansgar Lohse; Verena Krähling; Markus Eickmann; Stephan Becker; Selidji Todagbe Agnandji; Sanjeev Krishna; Peter G. Kremsner; Jessica S. Brosnahan; Philip Bejon; Patricia Njuguna; Marylyn M. Addo; Stephan Becker; Verena Krähling; Claire-Anne Siegrist; Angela Huttner; Marie-Paule Kieny; Vasee Moorthy; Patricia Fast; Barbara Savarese; Olivier Lapujade

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

2017

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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