title: Α1-giardin based live heterologous vaccine protects against Giardia lamblia infection in a murine model.
abstract: Giardia lamblia is a leading protozoan cause of diarrheal disease worldwide, yet preventive medical strategies are not available. A crude veterinary vaccine has been licensed for cats and dogs, but no defined human vaccine is available. We tested the vaccine potential of three conserved antigens previously identified in human and murine giardiasis, α1-giardin, α-enolase, and ornithine carbamoyl transferase, in a murine model of G. lamblia infection. Live recombinant attenuated Salmonella enterica Serovar Typhimurium vaccine strains were constructed that stably expressed each antigen, maintained colonization capacity, and sustained total attenuation in the host. Oral administration of the vaccine strains induced antigen-specific serum IgG, particularly IgG(2A), and mucosal IgA for α1-giardin and α-enolase, but not for ornithine carbamoyl transferase. Immunization with the α1-giardin vaccine induced significant protection against subsequent G. lamblia challenge, which was further enhanced by boosting with cholera toxin or sublingual α1-giardin administration. The α-enolase vaccine afforded no protection. Analysis of α1-giardin from divergent assemblage A and B isolates of G. lamblia revealed >97% amino acid sequence conservation and immunological cross-reactivity, further supporting the potential utility of this antigen in vaccine development. Together. These results indicate that α1-giardin is a suitable candidate antigen for a vaccine against giardiasis.
authors: Department of Medicine, University of California, San Diego, La Jolla, CA 92093, United States.
authors: Gabriela
authors: G
authors: Jenikova
authors: Petr
authors: P
authors: Hruz
authors: Mattias K
authors: MK
authors: Andersson
authors: Noa
authors: N
authors: Tejman-Yarden
authors: Patricia C D
authors: PC
authors: Ferreira
authors: Yolanda S
authors: YS
authors: Andersen
authors: Barbara J
authors: BJ
authors: Davids
authors: Frances D
authors: FD
authors: Gillin
authors: Staffan G
authors: SG
authors: Svärd
authors: Roy
authors: R
authors: Curtiss
authors: Lars
authors: L
authors: Eckmann
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000913:Antibodies, Protozoan / Q000096:biosynthesis; D000953:Antigens, Protozoan / Q000276:immunology; D002772:Cholera Toxin / Q000276:immunology; D003598:Cytoskeletal Proteins / Q000008:administration & dosage / Q000276:immunology*; D016829:Giardia lamblia / Q000276:immunology*; D005873:Giardiasis / Q000276:immunology / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D009954:Ornithine Carbamoyltransferase / Q000008:administration & dosage / Q000276:immunology; D010751:Phosphopyruvate Hydratase / Q000008:administration & dosage / Q000276:immunology; D015800:Protozoan Proteins / Q000008:administration & dosage / Q000276:immunology*; D016052:Protozoan Vaccines / Q000008:administration & dosage / Q000276:immunology*; D012486:Salmonella typhimurium / Q000235:genetics; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000276:immunology
chemical_list: D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D003598:Cytoskeletal Proteins; D015800:Protozoan Proteins; D016052:Protozoan Vaccines; D014614:Vaccines, Synthetic; C038207:giardin protein, Giardia lamblia; D002772:Cholera Toxin; D009954:Ornithine Carbamoyltransferase; D010751:Phosphopyruvate Hydratase