Chloroplast-derived therapeutic and prophylactic vaccines

Abstract

Despite the development of advanced vaccine technology, as many as 15 million deaths occur annually as a result of inadequate prophylactic or therapeutic treatments against infectious diseases (World Health Organization 2008). The emphasis on profitability by the pharmaceutical industry has led to development of high-cost vaccines targeting diseases with high profit margins, resulting in an annual death toll for developing countries that is largely preventable. Daniell and -co-investigators published the first expression of a vaccine antigen, cholera toxin subunit B, through transgenic tobacco chloroplasts in 2001. The polyploidy nature of the chloroplast genome enables engineering of a high copy number of target gene, while the translational machinery of the plastid directs the synthesis of bioactive proteins with proper folding, disulfide bond formation, and lipidation. Furthermore, gene integration is site-specific, expression is polycistronic, and natural gene containment occurs due to the maternal inheritance of the chloroplast genome. The chloroplast transformation technology (CTT) has been used to express proteins of bacterial, viral, protozoan, and recently mammalian origins that may be subsequently utilized in immunization strategies to produce protective or therapeutic immunity. Such chloroplast-derived vaccines represent an inexpensive and effective means of producing antigen-subunit vaccines. Furthermore, transformation of edible crops such as lettuce could generate stable orally-deliverable vaccine antigens through inexpensive field production and agricultural drying techniques. This platform could therefore obviate cold-chain logistics and the requirement of sterile injectables, drastically reducing downstream production costs of such biopharmaceuticals. With these proof-of-concept studies, focus within CTT is shifting towards establishing a viable platform for human immunization by demonstrating the -functionality of such chloroplast derived proteins, emphasizing the need to develop edible plant-based alternatives to tobacco, and improving efficacy through -additional peptide fusion-domains.