5 years ago

Enhancing Immune Responses to Cancer Vaccines Using Multi-Site Injections

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

Publisher URL: https://www.nature.com/articles/s41598-017-08665-9

DOI: 10.1038/s41598-017-08665-9

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