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

TitleLive attenuated yellow fever 17D infects human DCs and allows for presentation of endogenous and recombinant T cell epitopes.
Publication TypeJournal Article
Year of Publication2005
AuthorsBarba-Spaeth G, Longman RS, Albert ML, Rice CM
JournalJ Exp Med
Volume202
Issue9
Pagination1179-84
Date Published2005 Nov 7
ISSN0022-1007
KeywordsAntigen Presentation, Apoptosis, Calcium, Cells, Cultured, Dendritic Cells, Epitopes, T-Lymphocyte, Humans, T-Lymphocytes, Vaccines, Attenuated, Vaccines, Synthetic, Yellow Fever Vaccine, Yellow fever virus
Abstract

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.

DOI10.1084/jem.20051352
Alternate JournalJ. Exp. Med.
PubMed ID16260489
PubMed Central IDPMC2213233