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Infection and Immunity, September 2002, p. 4833-4840, Vol. 70, No. 9
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.9.4833-4840.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Coadministration of an Interleukin-12 Gene and a Trypanosoma cruzi Gene Improves Vaccine Efficacy

Department of Respiratory Medicine,¹ Department of Molecular and Cellular Parasitology,² Department of Immunology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421,³ Department of Tropical Medicine and Parasitology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582,⁴ Department of Veterinary Sciences, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan⁵

Received 1 April 2002/ Returned for modification 2 May 2002/ Accepted 29 May 2002

We tested the immunogenicity of two Trypanosoma cruzi antigens injected into mice in the form of DNA vaccine. Immunization with DNA encoding dihydroorotate dehydrogenase did not confer protective immunity in all mouse strains tested. Immunization with DNA encoding trans-sialidase surface antigen (TSSA) protected C57BL/6 (H-2^b) mice but not BALB/c (H-2^d) or C3H/Hej (H-2^k) mice against lethal T. cruzi infection. In vivo depletion of CD4⁺ or CD8⁺ T cells abolished the protective immunity elicited by TSSA gene in C57BL/6 mice. Enzyme-linked immunospot assay with splenocytes from T. cruzi-infected mice or TSSA gene-vaccinated mice identified an H-2K^b-restricted antigenic peptide, ANYNFTLV. The CD8⁺-T-cell line specific for this peptide could recognize T. cruzi-infected cells in vitro and could protect naive mice from lethal infection when adoptively transferred. Coadministration of the interleukin-12 (IL-12) gene with the TSSA gene facilitated the induction of ANYNFTLV-specific CD8⁺ T cells and improved the vaccine efficacy against lethal T. cruzi infection. These results reinforced the utility of immunomodulatory adjuvants such as IL-12 gene for eliciting protective immunity against intracellular parasites by DNA vaccination.

Editor: W. A. Petri, Jr.

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