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Heterologous Priming-Boosting with DNA and Modified Vaccinia Virus Ankara Expressing Tryparedoxin Peroxidase Promotes Long-Term Memory against Leishmania major in Susceptible BALB/c Mice

Cambridge Institute for Medical Research, University of Cambridge, Cambridge, CB2 2XY, United Kingdom,¹ Department of Medicine, University of Cambridge School of Clinical Medicine, Cambridge, CB2 2QQ, United Kingdom²

Received 18 September 2006/ Returned for modification 24 October 2006/ Accepted 7 November 2006

Leishmaniasis affects 12 million people, but there are no vaccines in routine clinical use. Th1 polarizing vaccines that elicit long-term protection are required to prevent disease in susceptible populations. We recently showed that heterologous priming-boosting with tryparedoxin peroxidase (TRYP) DNA followed by TRYP-modified vaccinia virus Ankara (TRYP MVA) protected susceptible BALB/c mice from Leishmania major. Here we compared treatment with TRYP DNA with treatment with TRYP DNA/TRYP MVA. We found that equivalent levels of protection during the postvaccination effector phase correlated with equivalent levels of serum immunoglobulin G2a and gamma interferon (IFN-) in draining lymph nodes. In contrast, challenge infection during the memory phase revealed that there was enhanced clinical efficacy with TRYP DNA/TRYP MVA. This correlated with higher levels of effector phase splenic IFN-, sustained prechallenge levels of memory phase IFN-, and a more polarized post-L. major challenge Th1 response compared to the Th2/T_reg response. Thus, TRYP DNA/TRYP MVA, but not TRYP DNA alone, provides long-term protection against murine leishmaniasis.

Published ahead of print on 13 November 2006.

Editor: W. A. Petri, Jr.