Da Silva, D.M.; Martinez, E.A.; Bogaert, L.; Kast, W.M. Investigation of the Optimal Prime Boost Spacing Regimen for a Cancer Therapeutic Vaccine Targeting Human Papillomavirus. Cancers2022, 14, 4339.
Da Silva, D.M.; Martinez, E.A.; Bogaert, L.; Kast, W.M. Investigation of the Optimal Prime Boost Spacing Regimen for a Cancer Therapeutic Vaccine Targeting Human Papillomavirus. Cancers 2022, 14, 4339.
Da Silva, D.M.; Martinez, E.A.; Bogaert, L.; Kast, W.M. Investigation of the Optimal Prime Boost Spacing Regimen for a Cancer Therapeutic Vaccine Targeting Human Papillomavirus. Cancers2022, 14, 4339.
Da Silva, D.M.; Martinez, E.A.; Bogaert, L.; Kast, W.M. Investigation of the Optimal Prime Boost Spacing Regimen for a Cancer Therapeutic Vaccine Targeting Human Papillomavirus. Cancers 2022, 14, 4339.
Abstract
Therapeutic vaccine studies should be designed to elicit durable, high magnitude, and efficacious T cell responses, all of which can be impacted by the choice of vaccination schedule. Here, we compare different prime-boost intervals (PBI) in a human papillomavirus (HPV) model using HPV16E6E7 Venezuelan equine encephalitis virus replicon particle (VRP) vaccination to address the optimal boosting schedule, quality of immune response, and overall in vivo efficacy. Six different vaccine regimens were tested with each group receiving booster vaccinations at different time intervals. Analysis of T-cell responses demonstrated a significant HPV16 E7 specific CD8+T cell response with minimally a one-week PBI between antigen re-exposure. Significant E7-specific in vivo cytotoxicity was also observed with longer PBIs. Additionally, longer PBIs led to an enhanced memory recall response to tumor challenge, which correlated with differential expansion of T cell memory subsets. Our findings imply that when using alphavirus vector platforms as a vaccination strategy, a one-week PBI is sufficient to induce high magnitude effector T cells with potent anti-tumor activity. However, longer PBIs lead to enhanced long-term protective anti-tumor immunity. These findings have implications for therapeutic vaccine clinical trials in which shorter intervals of prime-boost regimens may lead to suboptimal durable immune responses.
Keywords
prime-boost immunization; tumor immunity; T cell memory; cytotoxic T cells; therapeutic vaccine
Subject
Biology and Life Sciences, Immunology and Microbiology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
