Inducing efficient cross-priming using antigen-coated yeast particles Journal Article
| Authors: | Howland, S. W.; Tsuji, T.; Gnjatic, S.; Ritter, G.; Old, L. J.; Wittrup, K. D. |
| Article Title: | Inducing efficient cross-priming using antigen-coated yeast particles |
| Abstract: | Saccharomyces cerevisiae stimulates dendritic cells (DCs) and represents a promising candidate for cancer vaccine development. Effective cross-presentation of antigen delivered to DCs is necessary for successful induction of cellular immunity. Here, we present a yeast-based vaccine approach that is independent of yeast's ability to express the chosen antigen, which is instead produced separately and conjugated to the yeast cell wall. The conjugation method is site-specific (based on the SNAP-tag) and designed to facilitate antigen release in the DC phagosome and subsequent translocation for cross-presentation. We demonstrate that nonsite-specific chemical conjugation of the same protein hinders cross-presentation. Phagosomal antigen release was further expedited through the insertion of the invariant chain ectodomain as a linker, which is rapidly cleaved by Cathepsin S. The dose of delivered antigen was increased in several ways: by using yeast strains with higher surface amine densities, by using yeast hulls (cell wall fragments) instead of whole cells, and by conjugating multiple layers of antigen. The novel multilayer conjugation scheme takes advantage of Sfp phosphopantetheinyl transferase and remains site-specific; it enables the antigen dose to grow linearly with the number of layers. We show that whole yeast cells coated with 1 layer of the cancer-testis antigen NY-ESO-1 and yeast hulls bearing 3 layers were able to cross-prime naive CD8+ T cells in vitro, with the latter resulting in higher frequencies of antigen-specific cells after 10 days. This cross-presentation- efficient antigen conjugation scheme is not limited to yeast and can readily be applied toward the development of other particulate vaccines. © 2008 by Lippincott Williams and Wilkins. |
| Keywords: | controlled study; unclassified drug; human cell; genetics; nonhuman; cd8 antigen; antigen expression; cd8+ t lymphocyte; cd8-positive t-lymphocytes; metabolism; cell maturation; dendritic cell; membrane proteins; cell differentiation; drug potency; in vitro study; immunoreactivity; tumor antigen; antigen presentation; immunology; lymphocyte activation; dendritic cells; amine; cell wall; chemistry; hybrid protein; antigens, neoplasm; recombinant fusion proteins; gamma interferon; cancer vaccine; cancer vaccines; saccharomyces cerevisiae; ny eso 1 antigen; escherichia coli; hla antigen class 2; peptide fragments; ctag1b protein, human; membrane protein; peptide fragment; protein transport; testis tumor; testicular neoplasms; phosphoproteins; virus antigen; methylated dna protein cysteine methyltransferase; interferon-gamma; yeast; amination; microbiology; cytokine release; histocompatibility antigens class ii; phagosome; cytomegalovirus matrix protein 65kda; matrix protein; phosphoprotein; cytomegalovirus; viral matrix proteins; interleukin 12; drug conjugation; yeast cell; secretion; virus protein; drug release; immunization; conjugation; fungal strain; cathepsin s; coated vesicle; o(6)-methylguanine-dna methyltransferase; antigens, viral; cross presentation; cross-priming; transferase; cross-presentation; cd74 antigen; lymphocyte antigen; pantetheine phosphate; protein snap tag; b lymphocyte antigen; coated particle; interferon production; invariant chain; antigens, differentiation, b-lymphocyte; coated vesicles |
| Journal Title: | Journal of Immunotherapy |
| Volume: | 31 |
| Issue: | 7 |
| ISSN: | 1524-9557 |
| Publisher: | Lippincott Williams & Wilkins |
| Date Published: | 2008-09-01 |
| Start Page: | 607 |
| End Page: | 619 |
| Language: | English |
| DOI: | 10.1097/CJI.0b013e318181c87f |
| PUBMED: | 18600183 |
| PROVIDER: | scopus |
| PMCID: | PMC2820298 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 4" - "Export Date: 17 November 2011" - "CODEN: JOIME" - "Source: Scopus" |
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