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Infection and Immunity, September 2005, p. 6017-6025, Vol. 73, No. 9
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.9.6017-6025.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

CD8+-T-Cell-Dependent Control of Trypanosoma cruzi Infection in a Highly Susceptible Mouse Strain after Immunization with Recombinant Proteins Based on Amastigote Surface Protein 2

Adriano F. S. Araújo,1,2 Bruna C. G. de Alencar,1,2 José Ronnie C. Vasconcelos,1,2 Meire I. Hiyane,1,2 Cláudio R. F. Marinho,3 Marcus L. O. Penido,4 Silvia B. Boscardin,2 Daniel F. Hoft,5 Ricardo T. Gazzinelli,4 and Mauricio M. Rodrigues1,2*

Centro Interdisciplinar de Terapia Gênica (CINTERGEN),1 Departmento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de São Paulo-Escola Paulista de Medicina,2 Departamento de Imunologia, ICB, Av. Prof. Lineu Prestes, 1730, Universidade de São Paulo, São Paulo, SP 05508-900,3 Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais e Centro de Pesquisas René Rachou, FIOCRUZ, Avenida Augusto de Lima 1715, Barro Preto, 30190-002, Belo Horizonte, Minas Gerais, Brazil,4 Division of Infectious Diseases & Immunology, Departments of Internal Medicine & Molecular Microbiology, Saint Louis University Health Sciences Center, 3635 Vista Avenue, FDT-8N, St. Louis, Missouri 631105

Received 4 April 2005/ Returned for modification 6 May 2005/ Accepted 11 May 2005

We previously described that DNA vaccination with the gene encoding amastigote surface protein 2 (ASP-2) protects approximately 65% of highly susceptible A/Sn mice against the lethal Trypanosoma cruzi infection. Here, we explored the possibility that bacterial recombinant proteins of ASP-2 could be used to improve the efficacy of vaccinations. Initially, we compared the protective efficacy of vaccination regimens using either a plasmid DNA, a recombinant protein, or both sequentially (DNA priming and protein boosting). Survival after the challenge was not statistically different among the three mouse groups and ranged from 53.5 to 75%. The fact that immunization with a recombinant protein alone induced protective immunity revealed the possibility that this strategy could be pursued for vaccination. We investigated this possibility by using six different recombinant proteins representing distinct portions of ASP-2. The vaccination of mice with glutathione S-transferase fusion proteins representing amino acids 261 to 500 or 261 to 380 of ASP-2 in the presence of the adjuvants alum and CpG oligodeoxynucleotide 1826 provided remarkable immunity, consistently protecting 100% of the A/Sn mice. Immunity was completely reversed by the in vivo depletion of CD8+ T cells, but not CD4+ T cells, and was associated with the presence of CD8+ T cells specific for an epitope located between amino acids 320 and 327 of ASP-2. We concluded that a relatively simple formulation consisting of a recombinant protein with a selected portion of ASP-2, alum, and CpG oligodeoxynucleotide 1826 might be used to cross-prime strong CD8+-T-cell-dependent protective immunity against T. cruzi infection.

* Corresponding author. Mailing address: CINTERGEN, UNIFESP—Escola Paulista de Medicina, Rua Mirassol, 207, São Paulo-SP 04044-010, Brazil. Phone and fax: (55) (11) 5571-1095. E-mail: mrodrigues{at}ecb.epm.br.

Editor: W. A. Petri, Jr.

Infection and Immunity, September 2005, p. 6017-6025, Vol. 73, No. 9
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.9.6017-6025.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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