DNA and modified vaccinia Ankara prime–boost vaccination generates strong CD8 + T cell responses against minor histocompatibility antigen HA‐1

Autor: Jusnara Begum, Suzy A Eldershaw, Jane Nunnick, Hayden Pearce, Shamyla Saddique, Wayne Croft, Karen Piper, Ram Malladi, Graham P. Taylor, Ben Abbotts, Christine Stephens, Donna L Walsh, Mirjana Sirovica, Paul Ferguson, Samantha Nicol, Richard Powell, Sandeep Nagra, Charlotte F. Inman, Paul Moss
Rok vydání: 2021
Předmět:
Zdroj: British Journal of Haematology. 195:433-446
ISSN: 1365-2141
0007-1048
Popis: 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.
Databáze: OpenAIRE
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