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Infection and Immunity, August 2004, p. 4924-4928, Vol. 72, No. 8
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.8.4924-4928.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

DNA-Salmonella enterica Serovar Typhimurium Primer-Booster Vaccination Biases towards T Helper 1 Responses and Enhances Protection against Leishmania major Infection in Mice

Uta G. Lange,1,2 Pietro Mastroeni,3 Jenefer M. Blackwell,1,2* and Carmel B. Stober1,2

Cambridge Institute for Medical Research, University of Cambridge, Cambridge CB2 2XY,1 Department of Medicine, University of Cambridge School of Clinical Medicine, Cambridge CB2 2QQ,2 Centre for Veterinary Science, University of Cambridge, Cambridge CB3 0ES, United Kingdom3

Received 19 February 2004/ Returned for modification 23 March 2004/ Accepted 9 April 2004

Successful resolution of infections by intracellular pathogens requires gamma interferon (IFN-{gamma}). DNA vaccines promote T helper 1 (Th1) responses by triggering interleukin-12 (IL-12) release by dendritic cells (DC) through Toll-like receptor 9 (TLR9). In humans TLR9 is restricted to plasmacytoid DC. Here we show that DNA-Salmonella enterica serovar Typhimurium primer-booster vaccination, which provides alternative ligands to bind TLR4 on myeloid DC, strongly biases towards Th1 responses compared to vaccination with DNA alone. This results in higher immunoglobulin G2a (IgG2a) responses compared to IgG1 responses, higher IFN-{gamma} responses compared to IL-10 CD4+-T-cell responses, and enhanced protection against Leishmania major infection in susceptible BALB/c mice.

* Corresponding author. Mailing address: Cambridge Institute for Medical Research, Wellcome Trust/MRC Building, Addenbrooke's Hospital, Hills Rd., Cambridge CB2 2XY, United Kingdom. Phone: 44 1223 336143. Fax: 44 1223 331206. E-mail: jennie.blackwell{at}cimr.cam.ac.uk.

Editor: W. A. Petri, Jr.

Infection and Immunity, August 2004, p. 4924-4928, Vol. 72, No. 8
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.8.4924-4928.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Tuon, F. F., Amato, V. S., Bacha, H. A., AlMusawi, T., Duarte, M. I., Amato Neto, V. (2008). Toll-Like Receptors and Leishmaniasis. Infect. Immun. 76: 866-872 [Full Text]  
  • Chinchilla, M., Pasetti, M. F., Medina-Moreno, S., Wang, J. Y., Gomez-Duarte, O. G., Stout, R., Levine, M. M., Galen, J. E. (2007). Enhanced Immunity to Plasmodium falciparum Circumsporozoite Protein (PfCSP) by Using Salmonella enterica Serovar Typhi Expressing PfCSP and a PfCSP-Encoding DNA Vaccine in a Heterologous Prime-Boost Strategy. Infect. Immun. 75: 3769-3779 [Abstract] [Full Text]  


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