| Autor: |
Hofer T; Institute of Virology, Medical University of Innsbruck, A-6020 Innsbruck, Austria.; Christian Doppler Laboratory for Viral Immunotherapy of Cancer, A-6020 Innsbruck, Austria., Pipperger L; Institute of Virology, Medical University of Innsbruck, A-6020 Innsbruck, Austria.; Christian Doppler Laboratory for Viral Immunotherapy of Cancer, A-6020 Innsbruck, Austria.; Department of Internal Medicine V, Haematology & Oncology, Medical University Innsbruck, A-6020 Innsbruck, Austria.; Tyrolean Cancer Research Institute, A-6020 Innsbruck, Austria., Danklmaier S; Institute of Virology, Medical University of Innsbruck, A-6020 Innsbruck, Austria.; Christian Doppler Laboratory for Viral Immunotherapy of Cancer, A-6020 Innsbruck, Austria.; Tyrolean Cancer Research Institute, A-6020 Innsbruck, Austria., Das K; Institute of Virology, Medical University of Innsbruck, A-6020 Innsbruck, Austria.; Christian Doppler Laboratory for Viral Immunotherapy of Cancer, A-6020 Innsbruck, Austria.; ViraTherapeutics GmbH, A-6063 Rum, Austria., Wollmann G; Institute of Virology, Medical University of Innsbruck, A-6020 Innsbruck, Austria.; Christian Doppler Laboratory for Viral Immunotherapy of Cancer, A-6020 Innsbruck, Austria.; Department of Internal Medicine V, Haematology & Oncology, Medical University Innsbruck, A-6020 Innsbruck, Austria.; Tyrolean Cancer Research Institute, A-6020 Innsbruck, Austria. |
| Abstrakt: |
Numerous factors influence the magnitude and effector phenotype of vaccine-induced CD8 + T cells, thereby potentially impacting treatment efficacy. Here, we investigate the effect of vaccination dose, route of immunization, presence of a target antigen-expressing tumor, and heterologous prime-boost with peptide vaccine partner following vaccination with antigen-armed VSV-GP. Our results indicate that a higher vaccine dose increases antigen-specific CD8 + T cell proportions while altering the phenotype. The intravenous route induces the highest proportion of antigen-specific CD8 + T cells together with the lowest anti-viral response followed by the intraperitoneal, intramuscular, and subcutaneous routes. Moreover, the presence of a B16-OVA tumor serves as pre-prime, thereby increasing OVA-specific CD8 + T cells upon vaccination and thus altering the ratio of anti-tumor versus anti-viral CD8 + T cells. Interestingly, tumor-specific CD8 + T cells exhibit a different phenotype compared to bystander anti-viral CD8 + T cells. Finally, the heterologous combination of peptide and viral vaccine elicits the highest proportion of antigen-specific CD8 + T cells in the tumor and tumor-draining lymph nodes. In summary, we provide a basic immune characterization of various factors that affect anti-viral and vaccine target-specific CD8 + T cell proportions and phenotypes, thereby enhancing our vaccinology knowledge for future vaccine regimen designs. |
