Activation-induced Markers Detect Vaccine-Specific CD4+ T Cell Responses Not Measured by Assays Conventionally Used in Clinical Trials
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 smal...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2018-07-01
|
| Series: | Vaccines |
| Subjects: | |
| Online Access: | http://www.mdpi.com/2076-393X/6/3/50 |
| _version_ | 1811300890907246592 |
|---|---|
| author | Georgina Bowyer Tommy Rampling Jonathan Powlson Richard Morter Daniel Wright Adrian V.S. Hill Katie J. Ewer |
| author_facet | Georgina Bowyer Tommy Rampling Jonathan Powlson Richard Morter Daniel Wright Adrian V.S. Hill Katie J. Ewer |
| author_sort | Georgina Bowyer |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-13T06:58:03Z |
| format | Article |
| id | doaj.art-b0d8d3805861473aae29e13c8708410a |
| institution | Directory Open Access Journal |
| issn | 2076-393X |
| language | English |
| last_indexed | 2024-04-13T06:58:03Z |
| publishDate | 2018-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Vaccines |
| spelling | doaj.art-b0d8d3805861473aae29e13c8708410a2022-12-22T02:57:11ZengMDPI AGVaccines2076-393X2018-07-01635010.3390/vaccines6030050vaccines6030050Activation-induced Markers Detect Vaccine-Specific CD4+ T Cell Responses Not Measured by Assays Conventionally Used in Clinical TrialsGeorgina Bowyer0Tommy Rampling1Jonathan Powlson2Richard Morter3Daniel Wright4Adrian V.S. Hill5Katie J. Ewer6The Jenner Institute, University of Oxford, Oxford OX3 7DQ, UKThe Jenner Institute, University of Oxford, Oxford OX3 7DQ, UKThe Jenner Institute, University of Oxford, Oxford OX3 7DQ, UKThe Jenner Institute, University of Oxford, Oxford OX3 7DQ, UKThe Jenner Institute, University of Oxford, Oxford OX3 7DQ, UKThe Jenner Institute, University of Oxford, Oxford OX3 7DQ, UKThe Jenner Institute, University of Oxford, Oxford OX3 7DQ, UKImmunogenicity 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.http://www.mdpi.com/2076-393X/6/3/50vaccinesactivation-induced markersantigen-specific T cellsviral vectoradenovirusmodified vaccinia virus AnkaraEbola |
| spellingShingle | Georgina Bowyer Tommy Rampling Jonathan Powlson Richard Morter Daniel Wright Adrian V.S. Hill Katie J. Ewer Activation-induced Markers Detect Vaccine-Specific CD4+ T Cell Responses Not Measured by Assays Conventionally Used in Clinical Trials Vaccines vaccines activation-induced markers antigen-specific T cells viral vector adenovirus modified vaccinia virus Ankara Ebola |
| title | Activation-induced Markers Detect Vaccine-Specific CD4+ T Cell Responses Not Measured by Assays Conventionally Used in Clinical Trials |
| title_full | Activation-induced Markers Detect Vaccine-Specific CD4+ T Cell Responses Not Measured by Assays Conventionally Used in Clinical Trials |
| title_fullStr | Activation-induced Markers Detect Vaccine-Specific CD4+ T Cell Responses Not Measured by Assays Conventionally Used in Clinical Trials |
| title_full_unstemmed | Activation-induced Markers Detect Vaccine-Specific CD4+ T Cell Responses Not Measured by Assays Conventionally Used in Clinical Trials |
| title_short | Activation-induced Markers Detect Vaccine-Specific CD4+ T Cell Responses Not Measured by Assays Conventionally Used in Clinical Trials |
| title_sort | activation induced markers detect vaccine specific cd4 t cell responses not measured by assays conventionally used in clinical trials |
| topic | vaccines activation-induced markers antigen-specific T cells viral vector adenovirus modified vaccinia virus Ankara Ebola |
| url | http://www.mdpi.com/2076-393X/6/3/50 |
| work_keys_str_mv | AT georginabowyer activationinducedmarkersdetectvaccinespecificcd4tcellresponsesnotmeasuredbyassaysconventionallyusedinclinicaltrials AT tommyrampling activationinducedmarkersdetectvaccinespecificcd4tcellresponsesnotmeasuredbyassaysconventionallyusedinclinicaltrials AT jonathanpowlson activationinducedmarkersdetectvaccinespecificcd4tcellresponsesnotmeasuredbyassaysconventionallyusedinclinicaltrials AT richardmorter activationinducedmarkersdetectvaccinespecificcd4tcellresponsesnotmeasuredbyassaysconventionallyusedinclinicaltrials AT danielwright activationinducedmarkersdetectvaccinespecificcd4tcellresponsesnotmeasuredbyassaysconventionallyusedinclinicaltrials AT adrianvshill activationinducedmarkersdetectvaccinespecificcd4tcellresponsesnotmeasuredbyassaysconventionallyusedinclinicaltrials AT katiejewer activationinducedmarkersdetectvaccinespecificcd4tcellresponsesnotmeasuredbyassaysconventionallyusedinclinicaltrials |