alpha 1-giardin based live heterologous vaccine protects against Giardia lamblia infection in a murine model

• 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, alpha 1-giardin, alpha-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 alpha 1-giardin and alpha-enolase, but not for ornithine carbamoyl transferase. Immunization with the alpha 1-giardin vaccine induced significant protection against subsequent G. lamblia challenge, which was further enhanced by boosting with cholera toxin or sublingual alpha 1-giardin administration. The alpha-enolase vaccine afforded no protection. Analysis of at alpha 1-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 alpha 1-giardin is a suitable candidate antigen for a vaccine against giardiasis.

Nyckelord

Giardiasis

Live oral vaccines

Animal models

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