Coadministration of an interleukin-12 gene and a Trypanosoma cruzi gene improves vaccine efficacy.
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.
Department of Respiratory Medicine, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.
Masaharu
M
Katae
Yasushi
Y
Miyahira
Kazuyoshi
K
Takeda
Hironori
H
Matsuda
Hideo
H
Yagita
Ko
K
Okumura
Tsutomu
T
Takeuchi
Tsuneo
T
Kamiyama
Akihiko
A
Ohwada
Yoshinosuke
Y
Fukuchi
Takashi
T
Aoki
D000595:Amino Acid Sequence; D000818:Animals; D000953:Antigens, Protozoan / Q000235:genetics; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002460:Cell Line; D014355:Chagas Disease / Q000276:immunology / Q000517:prevention & control; D000090722:Dihydroorotate Dehydrogenase; D000939:Epitopes / Q000235:genetics; D005260:Female; D017125:Genes, Protozoan; D006023:Glycoproteins / Q000235:genetics / Q000276:immunology; D007116:Immunization, Passive; D018664:Interleukin-12 / Q000235:genetics*; D008212:Lymphocyte Depletion; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D009439:Neuraminidase / Q000235:genetics / Q000276:immunology; D010088:Oxidoreductases / Q000235:genetics / Q000276:immunology; D044925:Oxidoreductases Acting on CH-CH Group Donors; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology; D016052:Protozoan Vaccines / Q000008:administration & dosage* / Q000235:genetics; D013045:Species Specificity; D014349:Trypanosoma cruzi / Q000201:enzymology / Q000235:genetics* / Q000276:immunology*; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000235:genetics
D000953:Antigens, Protozoan; D000090722:Dihydroorotate Dehydrogenase; D000939:Epitopes; D006023:Glycoproteins; D010446:Peptide Fragments; D016052:Protozoan Vaccines; D019444:Vaccines, DNA; D018664:Interleukin-12; D010088:Oxidoreductases; D044925:Oxidoreductases Acting on CH-CH Group Donors; C069715:trans-sialidase; D009439:Neuraminidase