Vaccination with replication-deficient recombinant adenoviruses encoding the main surface antigens of toxoplasma gondii induces immune response and protection against infection in mice.
We have generated recombinant adenoviruses encoding three genetically modified surface antigens (SAGs) of the parasite Toxoplasma gondii, that is, AdSAG1, AdSAG2, and AdSAG3. Modifications included the removal of their glycosylphosphatidylinositol (GPI) anchoring motifs and, in some cases, the exchange of the native signal peptide for influenza virus hemagglutinin signal sequence. Adenovirus immunization of BALB/c mice elicited potent antibody responses against each protein, displaying a significant bias toward a helper T cell type 1 (Th1) profile in animals vaccinated with AdSAG1. Furthermore, the presence of parasite-specific IFN-gamma-producing T cells was analyzed by proliferation assays and enzyme-linked immunospot assays in the same animals. Splenocytes from immunized mice secreted IFN-gamma after in vitro stimulation with tachyzoite lysate antigen or with a fraction enriched for membrane-purified GPI-anchored proteins (F3) from the T. gondii tachyzoite surface. Epitopes recognized by CD8+ T cells were identified in SAG1 and SAG3, but not SAG2, sequences, although this protein also induced a specific response. We also tested the capacity of the immune responses detected to protect mice against a challenge with live T. gondii parasites. Although no protection was observed against tachyzoites of the highly virulent RH strain, a significant reduction in cyst loads in the brain was observed in animals challenged with the P-Br strain. Thus, up to 80% of the cysts were eliminated from animals vaccinated with a mixture of the three recombinant viruses. Because adenoviruses seemed capable of inducing Th1-biased protective immune responses against T. gondii antigens, other parasite antigens should be tested alone or in combination with those described here to further develop a protective vaccine against toxoplasmosis.
Caetano
Bráulia C
BC
Laboratório de Imunoparasitologia, Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, 31270-901, Brazil.
Bruña-Romero
Oscar
O
Fux
Blima
B
Mendes
Erica A
EA
Penido
Marcus L O
ML
Gazzinelli
Ricardo T
RT
D000256:Adenoviridae; D000818:Animals; D000953:Antigens, Protozoan / Q000235:genetics* / Q000276:immunology; D005260:Female; D017353:Gene Deletion; D007110:Immunity, Active; D007111:Immunity, Cellular; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D015800:Protozoan Proteins / Q000235:genetics* / Q000276:immunology; D016052:Protozoan Vaccines / Q000235:genetics* / Q000276:immunology; D011995:Recombination, Genetic; D014122:Toxoplasma / Q000276:immunology*; D014124:Toxoplasmosis, Animal / Q000276:immunology* / Q000517:prevention & control; D014614:Vaccines, Synthetic / Q000235:genetics / Q000276:immunology; D014779:Virus Replication / Q000235:genetics
D000953:Antigens, Protozoan; D008562:Membrane Glycoproteins; D015800:Protozoan Proteins; D016052:Protozoan Vaccines; C047168:SAG1 antigen, Toxoplasma; C087692:SAG3 protein, Toxoplasma gondii; D014614:Vaccines, Synthetic; C067547:surface antigen P22, Toxoplasma