Immunogenicity of transgenic plant-derived hepatitis B surface antigen.

Abstract

The focus of the Children's Vaccine Initiative is to encourage the discovery of technology that will make vaccines more readily available to developing countries. Our strategy has been to genetically engineer plants so that they can be used as inexpensive alternatives to fermentation systems for production of subunit antigens. In this paper we report on the immunological response elicited in vivo by using recombinant hepatitis B surface antigen (rHBsAg) purified from transgenic tobacco leaves. The anti-hepatitis B response to the tobacco-derived rHBsAg was qualitatively similar to that obtained by immunizing mice with yeast-derived rHBsAg (commercial vaccine). Additionally, T cells obtained from mice primed with the tobacco-derived rHBsAg could be stimulated in vitro by the tobacco-derived rHBsAg, yeast-derived rHBsAg, and by a synthetic peptide that represents part of the a determinant located in the S region (139-147) of HBsAg. Further support for the integrity of the T-cell epitope of the tobacco-derived rHBsAg was obtained by testing the ability of the primed T cells to proliferate in vitro after stimulation with a monoclonal anti-idiotype and an anti-idiotype-derived peptide, both of which mimic the group-specific a determinant of HBsAg. In total, we have conclusively demonstrated that both B-and T-cell epitopes of HBsAg are preserved when the antigen is expressed in a transgenic plant.

Medical molecular farming: production of antibodies, biopharmaceuticals and edible vaccines in plants

“…Plant-expressed antigens have been shown to able to induce mucosal and serum immune responses when administered parenterally or orally to experimental animals and, in some test cases, they have offered protection against a subsequent pathogen challenge or challenge model 14,16,[19][20][21][22][23][24] . A few of these vaccine candidates have been successfully tested in clinical trials or, where appropriate, in commercial or native animal trials [25][26][27][28][29][30] .…”

Immunogenicity in humans of an edible vaccine for hepatitis B

“…Initial research on vaccine production in plants focused on expression of antigenic proteins to protect against pathogens that cause diarrhea, because oral immunization was likely to induce localized protection against enteric diseases (5)(6)(7)(8)(9)(10). Parallel studies showed that hepatitis B surface antigen (HBsAg) could be expressed in plants, and it was immunogenic when partially purified and injected into mice (11). Moreover, when mice were fed transgenic potato tubers expressing HBsAg, both primary and booster serum antibody responses were elicited (12).…”

Transformation of HBsAg (hepatitis B surface antigen) gene into tomato mediated by Agrobacterium tumefaciens

“…In comparison with the traditional expression systems, plant-derived hepatitis B vaccine has attracted the attention of the pharmaceutical industry for reasons of safety and economy (Walmsley & Arntzen 2000). In the experiment with mice and human beings, parenteral immunization of plantderived hepatitis B surface antigen stimulated B and T cell immune responses similar to those found with commercial yeast-derived hepatitis B vaccine (Thanavala et al 1995). So, it is feasible to produce hepatitis B vaccine via transgenic plants.…”