The Journal of Experimental Medicine
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Published 18 January 2005. doi:10.1084/jem.20041526
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 201, Number 2, 201-209
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ARTICLE

 Yellow fever 17D as a vaccine vector for microbial CTL epitopes : protection in a rodent malaria model



Deng Tao1, Giovanna Barba-Spaeth3, Urvashi Rai1, Victor Nussenzweig2, Charles M. Rice3, and Ruth S. Nussenzweig1

1 Department of Medical and Molecular Parasitology, Department of Pathology, New York University School of Medicine, New York, NY 10016
2 Michael Heidelberger Division, Department of Pathology, New York University School of Medicine, New York, NY 10016
3 Laboratory of Virology and Infectious Disease, The Rockefeller University, New York, NY 10021

CORRESPONDENCE Charles M. Rice: ricec{at}rockefeller.edu or Ruth S. Nussenzweig: ruth.nussenzweig{at}med.nyu.edu

The yellow fever vaccine 17D (17D) is safe, and after a single immunizing dose, elicits long-lasting, perhaps lifelong protective immunity. One of the major challenges facing delivery of human vaccines in underdeveloped countries is the need for multiple injections to achieve full efficacy. To examine 17D as a vector for microbial T cell epitopes, we inserted the H-2Kd–restricted CTL epitope of the circumsporozoite protein (CS) of Plasmodium yoelii between 17D nonstructural proteins NS2B and NS3. The recombinant virus, 17D-Py, was replication competent and stable in vitro and in vivo. A single subcutaneous injection of 105 PFU diminished the parasite burden in the liver by ~70%. The high level of protection lasted between 4 and 8 wk after immunization, but a significant effect was documented even 24 wk afterwards. Thus, the immunogenicity of a foreign T cell epitope inserted into 17D mimics some of the remarkable properties of the human vaccine. Priming with 17D-Py followed by boosting with irradiated sporozoites conferred sterile immunity to 90% of the mice. This finding indicates that the immune response of vaccine-primed individuals living in endemic areas could be sustained and magnified by the bite of infected mosquitoes.

Abbreviations used: 17D, yellow fever vaccine 17D; CS, circumsporozoite protein; EEF, exoerythrocytic stage; MVA, modified vaccinia virus Ankara; MOI, multiplicity of infection.

D. Tao and G. Barba-Spaeth contributed equally to this paper.


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