Cholera toxin activates nonconventional adjuvant pathways that induce protective CD8 T-cell responses after epicutaneous vaccination.

Authors:
Address: Center for Immunology, Department of Laboratory Medicine and Pathology, University of Minnesota Medical School, Minneapolis MN 55414, USA.
Journal:

Publication:

abstract

The ability to induce humoral and cellular immunity via antigen delivery through the unbroken skin (epicutaneous immunization, EPI) has immediate relevance for vaccine development. However, it is unclear which adjuvants induce protective memory CD8 T-cell responses by this route, and the molecular and cellular requirements for priming through intact skin are not defined. We report that Cholera toxin (CT) is superior to other adjuvants in its ability to prime memory CD8 T cells that control bacterial and viral challenges. Epicutaneous immunization with CT does not require engagement of classic toll-like receptor (TLR) and inflammasome pathways and, surprisingly, is independent of skin langerin-expressing cells (including Langerhans cells). However, CT adjuvanticity required type-I IFN sensitivity, participation of a Batf3-dependent dendritic cell (DC) population and engagement of CT with suitable gangliosides. Chemoenzymatic generation of CT-antigen fusion proteins led to efficient priming of the CD8 T-cell responses, paving the way for development of this immunization strategy as a therapeutic option.

Related Articles
Enhancement of the priming efficacy of DNA vaccines encoding dendritic cell-targeted antigens by synergistic toll-like receptor ligands.
BMC Immunol. 2009
Enhancement of the priming efficacy of DNA vaccines encoding dendritic cell-targeted antigens by synergistic toll-like receptor ligands.
Grossmann C, Tenbusch M, Nchinda G, Temchura V, Nabi G, Stone GW, Kornbluth RS, Uberla K. BMC Immunol. 2009 Aug 3; 10:43. Epub 2009 Aug 3.
Batf3-dependent CD11b(low/-) peripheral dendritic cells are GM-CSF-independent and are not required for Th cell priming after subcutaneous immunization.
PLoS One. 2011
Batf3-dependent CD11b(low/-) peripheral dendritic cells are GM-CSF-independent and are not required for Th cell priming after subcutaneous immunization.
Edelson BT, Bradstreet TR, Wumesh KC, Hildner K, Herzog JW, Sim J, Russell JH, Murphy TL, Unanue ER, Murphy KM. PLoS One. 2011; 6(10):e25660. Epub 2011 Oct 17.
CD8-deficient mice exhibit augmented mucosal immune responses and intact adjuvant effects to cholera toxin.
Immunology. 1996
CD8-deficient mice exhibit augmented mucosal immune responses and intact adjuvant effects to cholera toxin.
Hörnquist E, Grdic D, Mak T, Lycke N. Immunology. 1996 Feb; 87(2):220-9.
Defining the antigen-specific T-cell response to vaccination and poly(I:C)/TLR3 signaling: evidence of enhanced primary and memory CD8 T-cell responses and antitumor immunity.
J Immunother. 2005
Defining the antigen-specific T-cell response to vaccination and poly(I:C)/TLR3 signaling: evidence of enhanced primary and memory CD8 T-cell responses and antitumor immunity.
Salem ML, Kadima AN, Cole DJ, Gillanders WE. J Immunother. 2005 May-Jun; 28(3):220-8.
Review Dendritic cell-targeted protein vaccines: a novel approach to induce T-cell immunity.
J Intern Med. 2012
Review Dendritic cell-targeted protein vaccines: a novel approach to induce T-cell immunity.
Trumpfheller C, Longhi MP, Caskey M, Idoyaga J, Bozzacco L, Keler T, Schlesinger SJ, Steinman RM. J Intern Med. 2012 Feb; 271(2):183-92. Epub 2012 Jan 4.

To top • Home

TraveldoctorOnline 2001 • Disclaimer • webmaster

The contents within traveldoctoronline are presented only for informational purposes and cannot substitute for professional health care or any other medical treatment.All users of this website with health problems should be oblige always to consult their medical doctor before starting any treatment.