Enhancing Immune Responses to Cancer Vaccines Using Multi-Site Injections

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 pot...

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Autores principales:	Robert C. Mould, Amanda W. K. AuYeung, Jacob P. van Vloten, Leonardo Susta, Anthony J. Mutsaers, James J. Petrik, Geoffrey A. Wood, Sarah K. Wootton, Khalil Karimi, Byram W. Bridle
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/737148bd5cde45eb9e40820e34961971
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spelling	oai:doaj.org-article:737148bd5cde45eb9e40820e349619712021-12-02T12:32:59ZEnhancing Immune Responses to Cancer Vaccines Using Multi-Site Injections10.1038/s41598-017-08665-92045-2322https://doaj.org/article/737148bd5cde45eb9e40820e349619712017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-08665-9https://doaj.org/toc/2045-2322Abstract 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.Robert C. MouldAmanda W. K. AuYeungJacob P. van VlotenLeonardo SustaAnthony J. MutsaersJames J. PetrikGeoffrey A. WoodSarah K. WoottonKhalil KarimiByram W. BridleNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-8 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Robert C. Mould Amanda W. K. AuYeung Jacob P. van Vloten Leonardo Susta Anthony J. Mutsaers James J. Petrik Geoffrey A. Wood Sarah K. Wootton Khalil Karimi Byram W. Bridle Enhancing Immune Responses to Cancer Vaccines Using Multi-Site Injections
description	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.
format	article
author	Robert C. Mould Amanda W. K. AuYeung Jacob P. van Vloten Leonardo Susta Anthony J. Mutsaers James J. Petrik Geoffrey A. Wood Sarah K. Wootton Khalil Karimi Byram W. Bridle
author_facet	Robert C. Mould Amanda W. K. AuYeung Jacob P. van Vloten Leonardo Susta Anthony J. Mutsaers James J. Petrik Geoffrey A. Wood Sarah K. Wootton Khalil Karimi Byram W. Bridle
author_sort	Robert C. Mould
title	Enhancing Immune Responses to Cancer Vaccines Using Multi-Site Injections
title_short	Enhancing Immune Responses to Cancer Vaccines Using Multi-Site Injections
title_full	Enhancing Immune Responses to Cancer Vaccines Using Multi-Site Injections
title_fullStr	Enhancing Immune Responses to Cancer Vaccines Using Multi-Site Injections
title_full_unstemmed	Enhancing Immune Responses to Cancer Vaccines Using Multi-Site Injections
title_sort	enhancing immune responses to cancer vaccines using multi-site injections
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/737148bd5cde45eb9e40820e34961971
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Enhancing Immune Responses to Cancer Vaccines Using Multi-Site Injections

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