biostudies-literatureUnknown7(1)Mould RCCIHRFor 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.Scientific reports8322https://www.ebi.ac.uk/biostudies/studies/S-EPMC5559552biostudies-literatureEnhancing Immune Responses to Cancer Vaccines Using Multi-Site Injections.PMC5559552Mould RCKarimi KWootton SKPetrik JJMutsaers AJSusta LBridle BWvan Vloten JPAuYeung AWKWood GAfalseEnhancing Immune Responses to Cancer Vaccines Using Multi-Site Injections.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.2017-01-01T00:00:00Z2017 Aug2021-02-21T11:32:32Z2019-03-27T02:53:42ZS-EPMC55595522881473310.1038/s41598-017-08665-9