title: A DNA-priming protein-boosting regimen significantly improves type 1 immune response but not protective immunity to Trypanosoma cruzi infection in a highly susceptible mouse strain.
abstract: BALB/c or C57Bl/6 mice immunized with plasmids containing Trypanosoma cruzi genes developed specific immune responses and protective immunity against lethal parasitic infection. In contrast, in the highly susceptible mouse strain A/Sn, DNA vaccination reduced the peak parasitemia but promoted limited mouse survival after challenge. In the present study, we tested whether the immunogenicity and protective efficacy of vaccination could be improved by combining DNA and recombinant protein immunization regimens. A/Sn mice immunized with plasmid p154/13 which harbours the gene encoding Trypanosoma cruzi trans-sialidase developed a predominant type 1 immune response. In contrast, immunization with the recombinant Trypanosoma cruzi trans-sialidase protein adsorbed to alum generated a typical type 2 immune response. Simultaneous administration of both p154/13 and recombinant Trypanosoma cruzi trans-sialidase protein also led to a predominant type 2 immune response. Sequential immunization consisting of two priming doses of p154/13 followed by booster injections with recombinant Trypanosoma cruzi trans-sialidase protein significantly improved specific type 1 immune response, as revealed by a drastic reduction of the serum IgG1/IgG2a ratio and by an increase in the in vitro interferon-gamma secretion by CD4 T cells. Our observations confirm and extend previous data showing that a DNA-priming protein-boosting regimen might be a general strategy to enhance type 1 immune response to DNA vaccines. Upon challenge with Trypanosoma cruzi, no improvement in protective immunity was observed in mice immunized with the DNA-priming protein-boosting regimen when compared to animals that received DNA only. Therefore, our results suggest that in this experimental model there is no correlation between the magnitude of type 1 immune response and protective immunity against Trypanosoma cruzi infection.
authors.affiliation: Departamento de Microbiologia, Imunologia e Parasitologia, Centro de Terapia Gênica (Cintergen) Universidade Federal de São Paulo-Escola Paulista de Medicina, São Paulo, Brazil.
authors.forename: José Ronnie C
authors.initials: JR
authors.lastname: Vasconcelos
authors.forename: Silvia B
authors.initials: SB
authors.lastname: Boscardin
authors.forename: Meire I
authors.initials: MI
authors.lastname: Hiyane
authors.forename: Sheila S
authors.initials: SS
authors.lastname: Kinoshita
authors.forename: Adriana E
authors.initials: AE
authors.lastname: Fujimura
authors.forename: Mauricio M
authors.initials: MM
authors.lastname: Rodrigues
mesh_terms: D000818:Animals; D000917:Antibody Formation / Q000187:drug effects; D014355:Chagas Disease / Q000517:prevention & control / Q000628:therapy*; D016054:DNA, Protozoan / Q000627:therapeutic use; D004198:Disease Susceptibility; D006023:Glycoproteins; D007111:Immunity, Cellular / Q000187:drug effects; D007114:Immunization / Q000379:methods*; D051379:Mice; D008815:Mice, Inbred Strains; D009439:Neuraminidase / Q000008:administration & dosage / Q000235:genetics / Q000627:therapeutic use; D011994:Recombinant Proteins / Q000008:administration & dosage* / Q000627:therapeutic use; D015996:Survival Rate; D014349:Trypanosoma cruzi / Q000737:chemistry / Q000235:genetics; D019444:Vaccines, DNA / Q000008:administration & dosage*
chemical_list: D016054:DNA, Protozoan; D006023:Glycoproteins; D011994:Recombinant Proteins; D019444:Vaccines, DNA; C069715:trans-sialidase; D009439:Neuraminidase