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DNA and modified vaccinia Ankara prime–boost vaccination generates strong CD8+ T cell responses against minor histocompatibility antigen HA‐1.
- Source :
- British Journal of Haematology; Nov2021, Vol. 195 Issue 3, p433-446, 14p
- Publication Year :
- 2021
-
Abstract
- Summary: Allogeneic immune responses underlie the graft‐versus‐leukaemia effect of stem cell transplantation, but disease relapse occurs in many patients. Minor histocompatibility antigen (mHAg) peptides mediate alloreactive T cell responses and induce graft‐versus‐leukaemia responses when expressed on patient haematopoietic tissue. We vaccinated nine HA‐1‐negative donors against HA‐1 with a 'prime–boost' protocol of either two or three DNA 'priming' vaccinations prior to 'boost' with modified vaccinia Ankara (MVA). HA‐1‐specific CD8+ T cell responses were observed in seven donors with magnitude up to 1·5% of total CD8+ T cell repertoire. HA‐1‐specific responses peaked two weeks post‐MVA challenge and were measurable in most donors after 12 months. HA‐1‐specific T cells demonstrated strong cytotoxic activity and lysed target cells with endogenous HA‐1 protein expression. The pattern of T cell receptor (TCR) usage by HA‐1‐specific T cells revealed strong conservation of T cell receptor beta variable 7‐9 (TRBV7‐9) usage between donors. These findings describe one of the strongest primary peptide‐specific CD8+ T cell responses yet recorded to a DNA–MVA prime–boost regimen and this may reflect the strong immunogenicity of mHAg peptides. Prime–boost vaccination in donors or patients may prove of substantial benefit in boosting graft‐versus‐leukaemia responses. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00071048
- Volume :
- 195
- Issue :
- 3
- Database :
- Complementary Index
- Journal :
- British Journal of Haematology
- Publication Type :
- Academic Journal
- Accession number :
- 153299351
- Full Text :
- https://doi.org/10.1111/bjh.17495