Cell Reports (Aug 2017)

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

DOI
https://doi.org/10.1016/j.celrep.2017.08.023
Journal volume & issue
Vol. 20, no. 9
pp. 2251 – 2261

Abstract

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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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