Towards a practical and affordable oral papaya-based vaccine: A crucial tool for taeniasis cysticercosis control programs

Cysticercosis is a parasitic disease caused by Taenia solium which affects rurally bred pigs and humans in developing countries. The adult tapeworm parasite lives in the humans intestines, where it sheds thousands of eggs. Cysticercosis occurs after eggs are ingested by pigs or humans. In humans, cysticerci may cause neurocysticercosis, the most severe and frequent form of the human disease. In pigs, cysticerci can lodge in different tissues. Deficient hygiene, inadequate feces disposal, outdoor defecation, freely roaming pigs, and inadequate meat inspection promote transmission. Since pigs are indispensable intermediate host, it is conceivable to curb transmission by reducing pig cysticercosis through vaccination. A vaccine against porcine cysticercosis to be extensively used in non-developed countries must not only be immunologically effective, but must also be inexpensive and simple to administrate to millions of rustically bred pigs, which are renewed every year and are dispersed in thousands of villages across large and variable geographic territories. We developed an anti-cysticercosis vaccine (S3Pvac) composed by three peptides originally identified in Taenia crassiceps. The first version of S3Pvac synthetically produced reduced by 50% the percent of infected pigs, and by 97% the number of cysticerci established, as assessed in a field trial. In search of reducing vaccine production costs, a version of S3Pvac recombinantly expressed in filamentous phages was developed. An improved procedure was standardized for its scale-up production and inactivation. S3Pvac-phage reduced by 54% the number of cysticercotic pigs and by 87% the total number of cysticerci, based on necropsy studies, in a field trial that included 1,047 rural pigs of central Mexico. However, the parenteral administration of the vaccine was found to be a major logistic and economic difficulty, limiting its use in yearly nation's wide programs. Such vaccine requires a risky capture of wild roaming pigs by not less than three or four trained persons. On the other hand, an orally administered vaccine would elude these difficulties, since it could be delivered by the pigs' owners when fed. An oral vaccine has additional attractive features, especially for the prevention of mucosally transmitted parasites as Taenia solium. Transgenic plants are ideal systems to produce oral vaccines, since the walls of the plant cells may protect antigenic proteins from digestion in the intestinal tract, enabling them for effective presentation to mucosal-associated lymphoid tissues. Moreover, the expression of foreign proteins in transgenic plants or in cultured plant cells offers an inexpensive system for the massive production of a vaccine. Thus, the S3Pvac peptides were expressed in transgenic embryogenic papaya cells. The vaccine peptides were stably expressed and incorporated into the papaya nuclear genome by particle bombardment. Orally administered S3Pvac-papaya, composed by transgenic embryogenic cell lines pKETc126, pKETc19, and pKETc723, effectively protect against experimental murine cysticercosis and are immunogenic in pigs. A safe, easy and low-cost system based on the culture of the S3Pvac-papaya cell suspension is being optimizing for massively producing the vaccine. Altogether, results point to the feasibility of having a cost-effective oral vaccine field trial conducted in the near future.