Activation-induced Markers Detect Vaccine-Specific CD4+ T Cell Responses Not Measured by Assays Conventionally Used in Clinical Trials

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.

Reduced Ebola vaccine responses in CMV+ young adults is associated with expansion of CD57+KLRG1+ T cells

“…Therefore, an alternative assay measuring activation-induced markers (AIMs), was used to determine the frequency and phenotype of antigen-responsive cells samples from the UK cohort ( Fig. 4 A ), as demonstrated previously ( Dan et al, 2016 ; Havenar-Daughton et al, 2016 ; Bowyer et al, 2018 ).…”

“…The AIM assay was conducted in a similar way to previously published work ( Dan et al, 2016 ; Havenar-Daughton et al, 2016 ; Bowyer et al, 2018 ). PBMCs were thawed as for the T cell phenotyping assay.…”

T Cell Memory to Vaccination

“…The ability to measure memory T cells in association with vaccination [19] is important to establish a vaccine’s immunogenicity and may be a biomarker of efficacy by having a positive association with protection from infection and/or disease [3,4]. Important factors in the measurement of T cell responses are the methods of measurement, when to make these measurements, and in which locations.…”

Early Diagnosis of Pathogen Infection by Cell-Based Activation Immunoassay

“…Methods for the detection of specifically activated cells are also based on other cell characteristics, such as physical shape, Ca2+ mobilization and gene expression [6,36,37]. Activation-induced markers (AIM) were used to identify antigen-specific T cells in a cytokine-independent assay [38,39,40], to detect vaccine and natural infection-induced CD4 T cell responses. Using a different approach, electrical impedance was shown to detect physical and structural shape changes upon T cell activation within 10–30 min [41,42].…”