Open AccessEnhancing Immune Responses to Cancer Vaccines Using Multi-Site Injections
Author(s) -
Robert C. Mould,
Amanda W.K. AuYeung,
Jacob P. van Vloten,
Leonardo Susta,
Anthony J. Mutsaers,
Jim Petrik,
Geoffrey A. Wood,
Sarah K. Wootton,
Khalil Karimi,
Byram W. Bridle
Publication year - 2017
Publication title -
scientific reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.24
H-Index - 213
ISSN - 2045-2322
DOI - 10.1038/s41598-017-08665-9
Subject(s) - immune system , antigen , cancer vaccine , immunology , vaccination , cd8 , medicine , antibody , cytotoxic t cell , t cell , immunotherapy , tumor microenvironment , virology , biology , biochemistry , in vitro
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.