Activation-induce markers detect vaccine-specific CD4+ T cell responses not measured by assays conventionally used in clinical trials

Georgina Bowyer*, Tommy Rampling, Jonathan Powlson, Richard Morter, Daniel Wright, Adrian V.S. Hill, Katie J. Ewer

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)

Abstract

Immunogenicity of T cell-inducing vaccines, such as viral vectors or DNA vaccines and Bacillus Calmette-Guérin (BCG), are frequently assessed by cytokine-based approaches. While these are sensitive methods that have shown correlates of protection in various vaccine studies, they only identify a small proportion of the vaccine-specific T cell response. Responses to vaccination are likely to be heterogeneous, particularly when comparing prime and boost or assessing vaccine performance across diverse populations. Activation-induced markers (AIM) can provide a broader view of the total antigen-specific T cell response to enable a more comprehensive evaluation of vaccine immunogenicity. We tested an AIM assay for the detection of vaccine-specific CD4+ and CD8+ T cell responses in healthy UK adults vaccinated with viral vectored Ebola vaccine candidates, ChAd3-EBO-Z and MVA-EBO-Z. We used the markers, CD25, CD134 (OX40), CD274 (PDL1), and CD107a, to sensitively identify vaccine-responsive T cells. We compared the use of OX40+ CD25+ and OX40+ PDL1+ in CD4+ T cells and OX40+ CD25+ and CD25+ CD107a+ in CD8+ T cells for their sensitivity, specificity, and associations with other measures of vaccine immunogenicity. We show that activation-induced markers can be used as an additional method of demonstrating vaccine immunogenicity, providing a broader picture of the global T cell response to vaccination.

Original languageEnglish
Article number50
JournalVaccines
Volume6
Issue number3
DOIs
Publication statusPublished - Sep 2018
Externally publishedYes

Bibliographical note

Funding Information:
Acknowledgments: The clinical trial was supported by funding from an Enhancement Award to a Wellcome Trust Strategic Award (to AVSH as PI) co-funded by the UK Medical Research Council, the UK Department for International Development and the European and Developing Countries Clinical Trials Partnership, with additional funding from the NIHR Oxford Biomedical Research Centre. The MVA-EBO-Z vaccine was biomanufactured for these trials by Emergent Biosolutions under a contract from Oxford University with funding from the same Enhancement Award. We would like to acknowledge Navin Venkatraman’s contributions towards this manuscript. He helped to design the clinical trial and provided clinical support for the trial but sadly passed away before this manuscript was prepared and was therefore unable to review the final manuscript and fulfil the ICMJE recommendations and COPE standards for authorship.

Publisher Copyright:
© 2018 by the authors. Licensee MDPI, Basel, Switzerland.

Keywords

  • Activation-induced markers
  • Adenovirus
  • Antigen-specific T cells
  • Ebola
  • Modified vaccinia virus ankara
  • Vaccines
  • Viral vector

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