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Infection and Immunity, January 2002, p. 240-248, Vol. 70, No. 1
0019-9567/01/$04.00+0     DOI: 10.1128/IAI.70.1.240-248.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Bacterial Lipoprotein-Based Vaccines Induce Tumor Necrosis Factor-Dependent Type 1 Protective Immunity against Leishmania major

Javier Cote-Sierra,1,{dagger} Amin Bredan,1 Carmen M. Toldos,2 Benoit Stijlemans,1 Lea Brys,1 Pierre Cornelis,1 Manuel Segovia,2 Patrick de Baetselier,1 and Hilde Revets1*

Department of Immunology, Parasitology and Ultrastructure, Flanders Interuniversity Institute for Biotechnology, Vrije Universiteit Brussel, Sint Genesius Rode, Belgium,1 Departamento de Genética y Microbiología, Facultad de Medicina, Universidad de Murcia, Murcia, Spain2

Received 20 June 2001/ Returned for modification 1 August 2001/ Accepted 1 October 2001

Immunity against Leishmania major requires rapid induction of a type 1 immune response in which tumor necrosis factor alpha (TNF-{alpha}) plays an essential role. Hence, vaccination strategies that simulate the protective immune response found in hosts that have recovered from natural infection provide a rational approach to combat leishmaniasis. One method for optimizing the qualitative and quantitative immune responses after vaccination is to use an adjuvant. In this study we demonstrate that the OprI lipoprotein (L-OprI) from Pseudomonas aeruginosa induces a long-term cellular (gamma interferon [IFN-{gamma}]) and humoral (immunoglobulin G2a) type 1 immune response against a truncated 32-kDa version (COOHgp63) of the 63-kDa major cell surface glycoprotein gp63. By contrast, immunization with COOHgp63 either fused to OprI nonlipoprotein or with no adjuvant did not result in the induction of type 1 immune responses. The adjuvanticity of L-OprI is strongly dependent on its capacity to induce TNF-{alpha}, since generation of type 1 immune responses is clearly delayed and impaired in TNF-{alpha}-/- mice. Vaccination with L-OprICOOHgp63 fusion protein protected BALB/c mice against L. major infection for at least 19 weeks. Vaccinated mice were largely free of lesions or clearly controlled lesion size on termination of the experiment. The control of disease progression in mice vaccinated with L-OprICOOHgp63 was associated with enhancement of antigen-specific IFN-{gamma} production. These data indicate that bacterial lipoproteins constitute appropriate adjuvants to include in vaccines against diseases in which type 1 immune responses are important for protection.

* Corresponding author. Mailing address: Department of Immunology, Parasitology and Ultrastructure, Flanders Interuniversity Institute for Biotechnology, Vrije Universiteit Brussel, Paardenstraat 65, B-1640 Sint Genesius Rode, Belgium. Phone: 32 2 359 03 57. Fax: 32 2 359 03 59. E-mail: harevets{at}vub.ac.be.

Editor: J. D. Clements

{dagger} Present address: Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Md.

Infection and Immunity, January 2002, p. 240-248, Vol. 70, No. 1
0019-9567/01/$04.00+0     DOI: 10.1128/IAI.70.1.240-248.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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