The Journal of Experimental Medicine
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Published online 31 October 2005 doi:10.1084/jem.20051352
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 202, Number 9, 1179-1184
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BRIEF DEFINITIVE REPORT

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

Giovanna Barba-Spaeth1, Randy S. Longman1,2, Matthew L. Albert3,4, and Charles M. Rice1

1 Laboratory of Virology and Infectious Disease, Center for the Study of Hepatitis C, The Rockefeller University, New York, NY 10021
2 Cornell/Rockefeller/Sloan-Kettering Tri-Institutional MD-PhD Program, New York, NY 10021
3 Institut Pasteur, Avenir, 75015 Paris, France
4 Institut national de la santé et de la recherche médicale, Avenir, 75015 Paris, France

CORRESPONDENCE Charles M. Rice: ricec{at}rockefeller.edu

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 Ca2+ 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.

G. Barba-Spaeth and R.S. Longman contributed equally to this work.


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