{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T16:27:36Z","timestamp":1781540856833,"version":"3.54.5"},"reference-count":20,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2017,8,16]],"date-time":"2017-08-16T00:00:00Z","timestamp":1502841600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2017,8,16]],"date-time":"2017-08-16T00:00:00Z","timestamp":1502841600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>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<jats:sup>+<\/jats:sup> 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<jats:sup>+<\/jats:sup> T cells specific for a self-tumor antigen. Further, the number of tumor antigen-specific antibodies, as well CD8<jats:sup>+<\/jats:sup> 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.<\/jats:p>","DOI":"10.1038\/s41598-017-08665-9","type":"journal-article","created":{"date-parts":[[2017,8,10]],"date-time":"2017-08-10T08:11:21Z","timestamp":1502352681000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Enhancing Immune Responses to Cancer Vaccines Using Multi-Site Injections"],"prefix":"10.1038","volume":"7","author":[{"given":"Robert C.","family":"Mould","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda W. 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