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Infect. Immun. doi:10.1128/IAI.01490-06
Copyright (c) 2006, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Heterologous prime-boosting with DNA and modified vaccinia virus Anakara 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, UK.; Department of Medicine, University of Cambridge School of Clinical Medicine, Cambridge, CB2 2QQ, UK

^* To whom correspondence should be addressed. Email: jennie.blackwell{at}cimr.cam.ac.uk.

	Abstract

Leishmaniasis affects 12 million people but there are no vaccines in routine clinical use. Th1 polarising vaccines that elicit long term protection are required to prevent disease in susceptible populations. We recently showed that heterologous prime-boosting with tryparedoxin peroxidase (TRYP) DNA followed by TRYP modified vaccinia virus Ankara (MVA) protected susceptible BALB/c mice from L. major. Here, we compare TRYP DNA with TRYP DNA/TRYP MVA. We show that equivalent levels of protection during the post-vaccination effector phase correlate with equivalent serum IgG2a and IFN- in draining LN. In contrast, challenge infection during the memory phase revealed enhanced clinical efficacy with TRYP DNA/TRYP MVA. This correlated with higher effector phase splenic IFN-, sustained pre-challenge memory phase IFN-, and a more polarized post-L. major challenge Th1 compared to Th2/T_reg response. TRYP DNA/TRYP MVA, but not TRYP DNA alone, thereby provides long-term protection against murine leishmaniasis.