Reichenbach, Dawn
(2013)
The effects of host response and vaccine design on early signaling profiles of MUC1-specific T cells.
Doctoral Dissertation, University of Pittsburgh.
(Unpublished)
Abstract
Vaccines are beginning to be explored for cancer prevention. Since the time between vaccination and determination of efficacy is long, there is a need for predictive early biomarkers. Immunological endpoints that are determined weeks or months post vaccination are currently being evaluated as biomarkers of vaccine efficacy to replace disease outcome that could take years to assess. However, when multiple vaccines are available, waiting for the development of humoral and cellular immunity could still cause delays while an earlier assessment would allow a timely change to a more effective prevention modality. We hypothesize that early activation of signaling networks within T cells in response to immunization predicts the outcome of the immune response and may be used as a biomarker of vaccine efficacy. Applying the phospho-flow technique to primary T cells, we examined phosphorylation of proteins that shape activation, proliferation, and differentiation of MUC1 tumor antigen-specific CD4 T cells within the first 24 hours post immunization as candidate biomarkers. Previously, our lab has shown that a vaccine composed of a MUC1 peptide loaded on DC is more effective in eliciting T cell immunity than a vaccine composed of the same peptide plus adjuvant. Furthermore, both vaccines stimulate T cells more effectively in wildtype (WT) compared to MUC1.Tg mice. We examined if signaling events downstream of the TCR or through various cell proliferation and survival pathways could predict differential potential of these two vaccines in two different hosts as early as 3, 6, 12, and 24 hours post immunization. Signaling signatures obtained reflect primarily differences between vaccines rather than between the hosts. We demonstrate the feasibility of using this approach to evaluate a vaccine’s potential to elicit a desired response leading to better vaccine design.
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Details
| Item Type: |
University of Pittsburgh ETD
|
| Status: |
Unpublished |
| Creators/Authors: |
|
| ETD Committee: |
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| Date: |
28 February 2013 |
| Date Type: |
Publication |
| Defense Date: |
18 January 2013 |
| Approval Date: |
28 February 2013 |
| Submission Date: |
28 February 2013 |
| Access Restriction: |
No restriction; Release the ETD for access worldwide immediately. |
| Number of Pages: |
135 |
| Institution: |
University of Pittsburgh |
| Schools and Programs: |
School of Medicine > Immunology |
| Degree: |
PhD - Doctor of Philosophy |
| Thesis Type: |
Doctoral Dissertation |
| Refereed: |
Yes |
| Uncontrolled Keywords: |
phosphoflow, T cell signaling, MUC1 transgenic mice, biomarker |
| Date Deposited: |
28 Feb 2013 13:32 |
| Last Modified: |
15 Nov 2016 14:10 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/17578 |
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