Enhancing Immune Responses to Cancer Vaccines Using Multi-Site Injections Academic Article uri icon

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abstract

  • For a vaccine to be effective it must induce a sufficiently robust and specific immune response. Multi-site injection protocols can increase the titers of rabies virus-neutralizing antibodies. Hypothetically, spreading a vaccine dose across multiple lymphatic drainage regions could also potentiate T cell responses. We used a replication-deficient adenovirus serotype 5-vectored cancer vaccine targeting the melanoma-associated antigen dopachrome tautomerase. Clinically, high numbers of tumor-infiltrating CD8+ T cells are a positive prognostic indicator. As such, there is interest in maximizing tumor-specific T cell responses. Our findings confirm a positive correlation between the number of tumor-specific T cells and survival. More importantly, we show for the first time that using multiple injection sites could increase the number of vaccine-induced CD8+ T cells specific for a self-tumor antigen. Further, the number of tumor antigen-specific antibodies, as well CD8+ T cells specific for a foreign antigen could also be enhanced. Our results show that multi-site vaccination induces higher magnitude immune responses than a single-bolus injection. This provides a very simple and almost cost-free strategy to potentially improve the efficacy of any current and future vaccine. Broader clinical adoption of multi-site vaccination protocols for the treatment of cancers and infectious diseases should be given serious consideration.

authors

  • Mould, Robert C
  • AuYeung, Amanda WK
  • van Vloten, Jacob P
  • Susta, Leonardo
  • Mutsaers, Anthony J
  • Petrik, James
  • Wood, Geoffrey A
  • Wootton, Sarah K
  • Karimi, Khalil
  • Bridle, Byram W

publication date

  • December 2017