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The annual national treatment and productivity costs associated with infectious diseases in the United States exceed $120 billion. According to the World Health Organization/Food and Agriculture Organization of the United Nations, more than 30 million children born each year are not vaccinated against vaccine-preventable diseases, and more than 25% of all deaths worldwide are attributable to infectious diseases.
As Western societies seek avenues to promote the health benefits of fruits and vegetables, scientists around the globe have explored immunization potential through edible vaccines. Collaborative efforts among medical scientists, plant biologists, and food science specialists during the past 15 years continue to contribute to the development and delivery of effective vaccines (aka therapeutic proteins) using transgenic tomatoes, bananas, rice, corn, and potatoes, as well as tobacco.
A variety of factors suggest the time is right to pursue edible vaccine development. They include the recent scientifically unsubstantiated fears associated with thimerasol-containing measles/mumps/rubella vaccine and autism; the more than 1 million injuries and infections in patients and healthcare workers following classic needle-syringe vaccinations and jet gun injections; the cost of environmental errors; political complacency; and the inability to provide global immunizations despite valiant efforts by numerous public health initiatives.
Current oral vaccine preparations are either from attenuated or killed microorganisms that survive the hostile intestinal environment and promote a desirable immunological reaction. On the other hand, plant-derived vaccines have emerged from a variety of strategies to stimulate plants to express foreign proteins (antigens) from human pathogens. The pioneering work on edible vaccines by Charles Arntzen and Hugh Mason at Arizona State University contributed to the production of antigenic proteins from enterotoxigenic E. coli, Norwalk virus, and hepatitis B virus.
There are three strategies for the production of plant-derived vaccines that seem most promising. Those strategies include direct transformation of plants, utilization of plant viruses, and generation of mucosally-targeted fusion proteins. Plant-derived have several advantages, including the absence of contaminants like animal viruses and prions, high production capacity, and low production costs. These advantages have spurred research to enhance expression of desirable antigens. For example, a recombinant vaccine antigen, HBsAg, originally produced in transgenic tobacco, has been expressed at low levels in lettuce leaves and cherry tomatillos. Plant-based RNA viruses represent robust systems to express unfused antigens or small antigenic epitopes.
The Norwalk virus (NV), a prototype of human noroviruses and primary cause of acute gastroenteritis among adults on cruise ships and in developing countries, is a public health menace. As of this writing, a vaccine against norovirus infections is not available. Santi et al. recently developed a rapid and efficient system to express recombinant NV capsid protein using tobacco leaves. Studies among CD1 mice indicated an appropriate immune response following the oral administration of this protein.
Other examples include transgenic tomato fruit used to express F1-V antigen fusion protein against Yersinia pestis, the causative agent of plague. Transgenic tomatoes, through the introduction of a synthetic gene, were developed to express a multivalent vaccine against diphtheria-pertussis-tetanus (DPT). Transgenic rice was developed as a delivery system to express antigenic lipoprotein that combats Neisseria gonorrhoeae.
There remain many challenges and questions before commercializing plant-based vaccines. While there have been several small, successful human trials against Norwalk virus, hepatitis B virus, and enteric infections using potatoes and corn as the delivery vehicle, plant-derived vaccine development must address the following issues: antigen selection, efficiency of the model system, plant species for vaccine expression, delivery and dosing, safety, public perception and attitudes, quality control, and, of course, the regulatory maze.
Preventing emerging infectious diseases in the 21st century is a CDC priority in which the food industry can actively participate. This global public health effort combines the myriad of food science and technology disciplines and reinforces the importance of multiple disciplines uniting to focus on a significant issue of public health through better foods using plant-based expression systems directed against childhood diseases and emerging diseases.
References to the articles cited above are available from the authors.
by Roger Clemens, Dr.P.H.,
ETHorn, La Mirada, Calif.
by Peter Pressman, M.D.,
LCDR, Medical Corps, U.S. Navy