α1-giardin based live heterologous vaccine protects against Giardia lamblia infection in a murine model

• Published in: Vaccine Vol. 29; no. 51; pp. 9529 - 9537
• Main Authors: Jenikova, Gabriela, Hruz, Petr, Andersson, Mattias K., Tejman-Yarden, Noa, Ferreira, Patricia C.D., Andersen, Yolanda S., Davids, Barbara J., Gillin, Frances D., Svärd, Staffan G., Curtiss, Roy, Eckmann, Lars
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Ltd 28.11.2011; Elsevier
• Subjects: Administration, Oral; Allergy and Immunology; amino acid sequences; Animal models; Animals; Antibodies, Protozoan - biosynthesis; antigens; Antigens, Protozoan - immunology; Applied microbiology; Biological and medical sciences; blood serum; cats; cholera toxin; Cholera Toxin - immunology; cross reaction; Cytoskeletal Proteins - administration & dosage; Cytoskeletal Proteins - immunology; dogs; Fundamental and applied biological sciences. Psychology; Giardia lamblia; Giardia lamblia - immunology; Giardiasis; Giardiasis - immunology; Giardiasis - prevention & control; Human protozoal diseases; humans; immunization; immunoglobulin A; immunoglobulin G; Infectious diseases; Live oral vaccines; Medical sciences; Mice; Mice, Inbred BALB C; Microbiology; oral administration; ornithine; Ornithine Carbamoyltransferase - administration & dosage; Ornithine Carbamoyltransferase - immunology; Parasitic diseases; Parasitic diseases due to ciliates and flagellates; phosphopyruvate hydratase; Phosphopyruvate Hydratase - administration & dosage; Phosphopyruvate Hydratase - immunology; Protozoal diseases; Protozoan Proteins - administration & dosage; Protozoan Proteins - immunology; Protozoan Vaccines - administration & dosage; Protozoan Vaccines - immunology; Salmonella Typhimurium; Salmonella typhimurium - genetics; vaccine development; vaccines; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects); Vaccines, Synthetic - administration & dosage; Vaccines, Synthetic - immunology; OCT; VSP; Animal models; Live oral vaccines; ADI; Giardiasis; arginine deiminase; ornithine carbamoyl transferase; variable surface protein; Infection; Animal model; Protozoal disease; Digestive diseases; Intestinal disease; Vaccine; Parasitosis
• ISSN: 0264-410X; 1873-2518; 1873-2518
• DOI: 10.1016/j.vaccine.2011.09.126

► Giardia lamblia is a leading protozoan cause of diarrheal disease worldwide. ► Preventive medical strategies are not available against giardiasis. ► Immunization of mice with a live α1-giardin vaccine protected against infection. ► α1-giardin is highly conserved between divergent Giardia isolates. 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 IgG2A, 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.