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The yellow fever (YF) 17D vaccine is one of the most successful live attenuated vaccines available. A single immunization induces both long-lasting neutralizing antibody and YF-specific T cell responses. Surprisingly, the mechanism for this robust immunity has not been addressed. In light of several recent reports suggesting flavivirus interaction with dendritic cells (DCs), we investigated the mechanism of YF17D interaction with DCs and the importance of this interaction in generating T cell immunity. Our results show that YF17D can infect immature and mature human DCs. Viral entry is Ca(2+) dependent, but it is independent of DC-SIGN as well as multiple integrins expressed on the DC surface. Similar to infection of cell lines, YF infection of immature DCs is cytopathic. Although infection itself does not induce DC maturation in vitro, TNF-alpha-induced maturation protects DCs from YF-induced cytopathogenicity. Furthermore, we show that DCs infected with YF17D or YF17D carrying a recombinant epitope can process and present antigens for CD8(+) T cell stimulation. These findings offer insight into the immunologic mechanisms associated with the highly capable YF17D vaccine that may guide effective vaccine design.

Titel:	Live attenuated yellow fever 17D infects human DCs and allows for presentation of endogenous and recombinant T cell epitopes.
Autor/in / Beteiligte Person:	Barba-Spaeth, G ; Longman, RS ; Albert, ML ; Rice, CM
Link:	Full Text Finder (Volltext)
Zeitschrift:	The Journal of experimental medicine, Jg. 202 (2005-11-07), Heft 9, S. 1179-84
Veröffentlichung:	New York, NY : Rockefeller University Press, 2005
Medientyp:	academicJournal
ISSN:	0022-1007 (print)
DOI:	10.1084/jem.20051352
Schlagwort:	Apoptosis physiology Calcium physiology Cells, Cultured Dendritic Cells metabolism Dendritic Cells virology Epitopes, T-Lymphocyte genetics Epitopes, T-Lymphocyte metabolism Humans T-Lymphocytes metabolism Vaccines, Attenuated immunology Vaccines, Attenuated metabolism Vaccines, Synthetic immunology Vaccines, Synthetic metabolism Yellow Fever Vaccine genetics Yellow Fever Vaccine metabolism Yellow fever virus immunology Yellow fever virus metabolism Antigen Presentation immunology Dendritic Cells immunology Epitopes, T-Lymphocyte immunology T-Lymphocytes immunology Yellow Fever Vaccine immunology
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article; Research Support, Non-U.S. Gov't Language: English [J Exp Med] 2005 Nov 07; Vol. 202 (9), pp. 1179-84. <i>Date of Electronic Publication: </i>2005 Oct 31. MeSH Terms: Antigen Presentation / immunology ; Dendritic Cells / immunology ; Epitopes, T-Lymphocyte / immunology ; T-Lymphocytes / immunology ; Yellow Fever Vaccine / *immunology ; Apoptosis / physiology ; Calcium / physiology ; Cells, Cultured ; Dendritic Cells / metabolism ; Dendritic Cells / virology ; Epitopes, T-Lymphocyte / genetics ; Epitopes, T-Lymphocyte / metabolism ; Humans ; T-Lymphocytes / metabolism ; Vaccines, Attenuated / immunology ; Vaccines, Attenuated / metabolism ; Vaccines, Synthetic / immunology ; Vaccines, Synthetic / metabolism ; Yellow Fever Vaccine / genetics ; Yellow Fever Vaccine / metabolism ; Yellow fever virus / immunology ; Yellow fever virus / metabolism References: J Med Virol. 1998 Oct;56(2):159-67. (PMID: 9746073) ; Nature. 1998 Mar 19;392(6673):245-52. (PMID: 9521319) ; J Virol. 1999 Oct;73(10):8083-94. (PMID: 10482557) ; J Biol Chem. 2004 Dec 24;279(52):54533-41. (PMID: 15475343) ; J Exp Med. 2005 Jan 17;201(2):201-9. (PMID: 15657290) ; Science. 2005 Jan 28;307(5709):593-6. (PMID: 15591165) ; Nat Rev Immunol. 2005 Mar;5(3):215-29. (PMID: 15738952) ; Virology. 1999 Dec 5;265(1):83-95. (PMID: 10603320) ; J Virol. 2000 Oct;74(19):9197-205. (PMID: 10982366) ; Virology. 2002 Feb 1;293(1):151-63. (PMID: 11853408) ; J Infect Dis. 2003 Jan 15;187(2):165-78. (PMID: 12552441) ; J Exp Med. 2003 Apr 7;197(7):823-9. (PMID: 12682107) ; J Gen Virol. 2003 May;84(Pt 5):1261-8. (PMID: 12692292) ; EMBO Rep. 2003 Jul;4(7):723-8. (PMID: 12783086) ; J Infect Dis. 2003 Oct 15;188(8):1213-30. (PMID: 14551893) ; Wkly Epidemiol Rec. 2003 Oct 3;78(40):349-59. (PMID: 14569711) ; Bull World Health Organ. 1981;59(6):895-900. (PMID: 6978196) ; J Gen Virol. 1984 Oct;65 ( Pt 10):1637-44. (PMID: 6208313) ; Proc Natl Acad Sci U S A. 1987 Apr;84(7):2019-23. (PMID: 3470774) ; Nature. 1987 Apr 30-May 6;326(6116):881-2. (PMID: 2437457) ; Virology. 1989 Mar;169(1):100-9. (PMID: 2922923) ; Virology. 1992 May;188(1):160-7. (PMID: 1566570) ; J Clin Invest. 1994 Aug;94(2):797-807. (PMID: 8040335) ; J Immunol Methods. 1996 Sep 27;196(2):137-51. (PMID: 8841452) ; J Exp Med. 1997 Sep 15;186(6):813-23. (PMID: 9294136) ; J Exp Med. 1997 Nov 3;186(9):1603-8. (PMID: 9348319) ; J Infect Dis. 1998 Mar;177(3):774-8. (PMID: 9498462) ; J Exp Med. 1999 Mar 1;189(5):821-9. (PMID: 10049946) Substance Nomenclature: 0 (Epitopes, T-Lymphocyte) ; 0 (Vaccines, Attenuated) ; 0 (Vaccines, Synthetic) ; 0 (Yellow Fever Vaccine) ; SY7Q814VUP (Calcium) Entry Date(s): Date Created: 20051102 Date Completed: 20060104 Latest Revision: 20181113 Update Code: 20240513 PubMed Central ID: PMC2213233

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Live attenuated yellow fever 17D infects human DCs and allows for presentation of endogenous and recombinant T cell epitopes.