Genetic immunization with LYT1 or a pool of trans-sialidase genes protects mice from lethal Trypanosoma cruzi infection.
Genetic immunization with a limited set of genes has been demonstrated to be an effective means of protecting mice from a normally lethal challenge of Trypanosoma cruzi. The goal of this study was to expand the diversity of genes assessed as genetic vaccine candidates. Screening a T. cruzi amastigote cDNA expression library with anti-amastigote monoclonal antibodies resulted in the identification of two genes, the previously identified flagellar Ca(2+) binding protein, FCaBP, and a novel homologue of the adaptin AP-3 complex beta3 subunit, Tcbeta3. A third gene, LYT1, recently identified as a secreted T. cruzi protein involved in cell lysis and infectivity, and was selected. Although peptides from all three genes were found to be targets of cytotoxic T cell responses in chronically infected mice, only immunization with LYT1 protected mice from a normally lethal challenge of T. cruzi. As an alternative to testing individual T. cruzi genes as vaccines, pools of genes from the trans-sialidase (TS) and mucin families were assessed in vaccination studies. Immunization with pools of TS but not mucin genes provided protection against a normally lethal challenge of T. cruzi. This study demonstrates that the ability of T. cruzi proteins to elicit immune responses in infected hosts does not necessarily associate with the ability to induce protection and that both the products of single genes and multi-gene families may serve as effective vaccines.
Fralish
Bolyn H
BH
Department of Cellular Biology, Center for Tropical and Emerging Global Diseases, University of Georgia, Athens, GA 30602, USA. fralish@alphavax.com
Tarleton
Rick L
RL
D000818:Animals; D015153:Blotting, Western; D019556:COS Cells; D014355:Chagas Disease / Q000276:immunology / Q000401:mortality / Q000517:prevention & control*; D002522:Chlorocebus aethiops; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006023:Glycoproteins / Q000235:genetics / Q000276:immunology*; D007114:Immunization; D007371:Interferon-gamma / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D009077:Mucins / Q000235:genetics / Q000276:immunology; D009439:Neuraminidase / Q000235:genetics / Q000276:immunology*; D015800:Protozoan Proteins / Q000235:genetics / Q000276:immunology*; D016052:Protozoan Vaccines / Q000235:genetics / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014349:Trypanosoma cruzi / Q000235:genetics / Q000276:immunology*
D006023:Glycoproteins; C429281:LYT1 protein, Trypanosoma cruzi; D009077:Mucins; D015800:Protozoan Proteins; D016052:Protozoan Vaccines; D007371:Interferon-gamma; C069715:trans-sialidase; D009439:Neuraminidase