title: DNA vaccination with a gene encoding Toxoplasma gondii GRA6 induces partial protection against toxoplasmosis in BALB/c mice.
abstract: BACKGROUND
  Infection with the protozoan Toxoplasma gondii causes serious public health problems and is of great economic importance worldwide. Protection from acute toxoplasmosis is known to be mediated by CD8+ T cells, but the T. gondii antigens and host genes required for eliciting protective immunity have been poorly defined. The T. gondii dense granule protein 6 (GRA6), recently proved to be highly immunogenic and produces fully immune protection in T. gondii infected BALB/c mice with an H-2Ld gene. The CD8+ T cell response of H-2Ld mice infected by the T. gondii strain seemed to target entirely to a single GRA6 peptide HF10-H-2Ld complex.
  
  
  RESULTS
  To determine whether a GRA6-based DNA vaccine can elicit protective immune responses to T. gondii in BALB/c mice, we constructed a eukaryotic expression vector pcDNA3.1-HisGRA6 and tested its immunogenicity in a mouse model. BALB/c mice were vaccinated intramuscularly with three doses of GRA6 DNA and then challenged with a lethal dose of T. gondii RH strain tachyzoites. All immunized mice developed high levels of serum anti-GRA6 IgG antibodies, and in vitro splenocyte proliferation was strongly enhanced in mice adjuvanted with levamisole (LMS). Immunization with pcDNA3.1-HisGRA6 with LMS resulted in 53.3% survival of challenged BALB/c mice as compared to 40% survival of BALB/c without LMS. Additionally, immunized Kunming mice without an allele of H-2Ld failed to survive.
  
  
  CONCLUSIONS
  Our result supports the concept that the acquired immune response is MHC restricted. This study has a major implication for vaccine designs using a single antigen in a population with diverse MHC class I alleles.
authors: National Animal Protozoa Laboratory & College of Veterinary Medicine, China Agricultural University, Beijing 100193, China.
authors: Xi-Meng
authors: XM
authors: Sun
authors: Jun
authors: J
authors: Zou
authors: Elashram Saeed
authors: ES
authors: A A
authors: Wen-Chao
authors: WC
authors: Yan
authors: Xian-Yong
authors: XY
authors: Liu
authors: Xun
authors: X
authors: Suo
authors: Heng
authors: H
authors: Wang
authors: Qi-Jun
authors: QJ
authors: Chen
mesh_terms: D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D000953:Antigens, Protozoan / Q000235:genetics / Q000276:immunology*; D049109:Cell Proliferation; D004195:Disease Models, Animal; D005260:Female; D007117:Immunization, Secondary / Q000379:methods; D007074:Immunoglobulin G / Q000097:blood; D007273:Injections, Intramuscular; D007963:Leukocytes, Mononuclear / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D015800:Protozoan Proteins / Q000235:genetics / Q000276:immunology*; D016052:Protozoan Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D013154:Spleen / Q000276:immunology; D016019:Survival Analysis; D014124:Toxoplasmosis, Animal / Q000517:prevention & control*; D014611:Vaccination / Q000379:methods*; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*
chemical_list: D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; C095047:GRA6 protein, Toxoplasma gondii; D007074:Immunoglobulin G; D015800:Protozoan Proteins; D016052:Protozoan Vaccines; D019444:Vaccines, DNA