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

Autor: Eldershaw SA; Institute of Immunology and Immunotherapy, College of Medical and Dental Sciences, Birmingham, UK., Pearce H; Institute of Immunology and Immunotherapy, College of Medical and Dental Sciences, Birmingham, UK., Inman CF; Institute of Immunology and Immunotherapy, College of Medical and Dental Sciences, Birmingham, UK., Piper KP; Institute of Immunology and Immunotherapy, College of Medical and Dental Sciences, Birmingham, UK., Abbotts B; Institute of Immunology and Immunotherapy, College of Medical and Dental Sciences, Birmingham, UK., Stephens C; Institute of Immunology and Immunotherapy, College of Medical and Dental Sciences, Birmingham, UK., Nicol S; Institute of Immunology and Immunotherapy, College of Medical and Dental Sciences, Birmingham, UK., Croft W; Institute of Immunology and Immunotherapy, College of Medical and Dental Sciences, Birmingham, UK., Powell R; Institute of Immunology and Immunotherapy, College of Medical and Dental Sciences, Birmingham, UK., Begum J; Institute of Immunology and Immunotherapy, College of Medical and Dental Sciences, Birmingham, UK., Taylor G; Institute of Immunology and Immunotherapy, College of Medical and Dental Sciences, Birmingham, UK., Nunnick J; Cancer Research UK Clinical Trials Unit, University of Birmingham, Birmingham, UK., Walsh D; Cancer Research UK Clinical Trials Unit, University of Birmingham, Birmingham, UK., Sirovica M; Cancer Research UK Clinical Trials Unit, University of Birmingham, Birmingham, UK., Saddique S; Cancer Research UK Clinical Trials Unit, University of Birmingham, Birmingham, UK., Nagra S; Department of Haematology, Birmingham Health Partners, Queen Elizabeth Hospital, Birmingham, UK., Ferguson P; Department of Haematology, Birmingham Health Partners, Queen Elizabeth Hospital, Birmingham, UK., Moss P; Institute of Immunology and Immunotherapy, College of Medical and Dental Sciences, Birmingham, UK.; Department of Haematology, Birmingham Health Partners, Queen Elizabeth Hospital, Birmingham, UK., Malladi R; Institute of Immunology and Immunotherapy, College of Medical and Dental Sciences, Birmingham, UK.; Department of Haematology, Birmingham Health Partners, Queen Elizabeth Hospital, Birmingham, UK.
Jazyk: angličtina
Zdroj: British journal of haematology [Br J Haematol] 2021 Nov; Vol. 195 (3), pp. 433-446. Date of Electronic Publication: 2021 May 28.
DOI: 10.1111/bjh.17495
Abstrakt: 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.
(© 2021 British Society for Haematology and John Wiley & Sons Ltd.)
Databáze: MEDLINE
Externí odkaz: