Food biopharmaceuticals as part of a sustainable bioeconomy: Edible vaccines case study.

The lack of immunization in developing countries is undoubtedly the most serious consequence of the difficulty in accessing traditional vaccination systems. The World Health Organization (WHO) has aimed to find low-cost vaccines, which are accessible to the population and are easy to store and distribute without the need for refrigeration. There is literature support that orally administered edible vaccines are promising agents to reduce the incidence of diseases such as hepatitis and diarrhoea, especially in the developing world. This article focuses on the study of the suitability of edible vaccines as biopharmaceuticals in the context of the 2030 Agenda for Sustainable Development, allowing to comprehensively address both malnutrition and the degree of immunization, mainly in the child population in developing countries. This is embedded within the scope of a new concept promulgated by the UN and FAO called' Therapeutic Food' or 'Ready to Use Therapeutic Food'. Biopharmaceuticals such as edible processed vaccines have the potential to play an important role in increasing global health to achieve the 2030 - Sustainable Development Goals (SDGs), and beyond, as a solution to the dual problem of malnutrition and immunoprophylaxis as part of a sustainable bioeconomy. This article reviews their most promising applications, as well as the problems of a scientific and socioeconomic nature, including the complex current legislation that restricts their implementation.

Estimating the cost of cholera-vaccine delivery from the societal point of view: A case of introduction of cholera vaccine in Bangladesh.

Cholera is a major global public health problem that causes both epidemic and endemic disease. The World Health Organization recommends oral cholera vaccines as a public health tool in addition to traditional prevention practices and treatments in both epidemic and endemic settings. In many developing countries like Bangladesh, the major issue concerns the affordability of this vaccine. In February 2011, a feasibility study entitled, "Introduction of Cholera Vaccine in Bangladesh (ICVB)", was conducted for a vaccination campaign using inactivated whole-cell cholera vaccine (Shanchol) in a high risk area of Mirpur, Dhaka. Empirical data obtained from this trial was used to determine the vaccination cost for a fully immunized person from the societal perspective. A total of 123,661 people were fully vaccinated receiving two doses of the vaccine, while 18,178 people received one dose of the same vaccine. The total cost for vaccine delivery was US$ 492,238 giving a total vaccination cost per fully-vaccinated individual of US$ 3.98. The purchase cost of the vaccine accounted for 58% of the overall cost of vaccination. Attempts to reduce the per-dose cost of the vaccine are likely to have a large impact on the cost of similar vaccination campaigns in the future.

The next 15 years: taking plant-made vaccines beyond proof of concept.

Significant potential advantages are associated with the production of vaccines in transgenic plants; however, no commercial product has emerged. An analysis of the strengths, weaknesses, opportunities and threats for plant-made vaccine technology is provided. The use of this technology for human vaccines will require significant investment and developmental efforts that cannot be supported entirely by the academic sector and is not currently supported financially by industry. A focus on downstream aspects to define potential products, conduct of additional basic clinical testing, and the incorporation of multidisciplinary strategic planning would accelerate the potential for commercialization in this field. Estimates of production cost per dose and volume of production are highly variable for a model vaccine produced in transgenic tomato, and can be influenced by the optimization of many factors. Commercialization of plant-made vaccine technology is likely to be led by the agricultural biotechnology sector rather than the pharmaceutical sector due to the disruptive nature of the technology and the complex intellectual property landscape. The next major milestones will be conduct of a phase II human clinical trial and demonstration of protection in humans. The achievement of these milestones would be accelerated by further basic investigation into mucosal immunity, the codevelopment of oral adjuvants, and the integration of quality control standards and good manufacturing practices for the production of preclinical and clinical batch materials.

Oral hepatitis B vaccine candidates produced and delivered in plant material.

Hepatitis B is a major global health problem; approximately two billion people are infected with the virus worldwide, despite the fact that safe and efficacious vaccines have been developed and used for nearly 20 years. Prohibitive costs for vaccine purchase and administration restrict uptake in many developing nations. Agencies such as the Global Alliance for Vaccination and Immunization are helping to make current vaccines more available, but reduced costs would greatly aid this effort. Oral delivery is an option to reduce the expense of administering hepatitis B vaccines. It may also improve compliance, and orally delivered vaccines may be more efficacious among poor responders to current vaccines. However, to induce protective efficacy, oral administration may require encapsulation of antigen and delivery of large doses. Plant-based expression systems offer an oral delivery alternative with low production costs, and they also encapsulate the antigen. Some plant-based systems also stabilize antigen and therefore reduce storage and distribution costs. The hepatitis B major surface antigen has been expressed in several plant systems. A variety of regulatory sequences and subcellular targets have been used to achieve expression suitable for early stage clinical trials. However, further increase in expression will be necessary for practical and efficacious products. Appropriate processing can yield palatable products with uniform antigen concentration. The antigen expressed in plant systems shows extensive disulphide cross-linking and oligomerization and forms virus-like particles. Oral delivery of the antigen in plant material can induce a serum antibody response, prime the immune system for a subsequent injection of antigen and give a boosted response to a prior injection. Small scale clinical trials in which the antigen has been delivered orally in edible plant material indicate safety and immunogenicity.

Garden-variety vaccines: antigens derived from transgenic plants.

The discovery of new vaccines can result from deletion of virulence determinants from a specific pathogen or from identification of target antigens that stimulate a protective immune response. Vaccine development will become less empirical as applications of genomics, proteomics and reverse vaccinology are exploited, and new protective antigens will emerge for inclusion in the vaccines of the future. However, production and purification of these new antigens for oral and parenteral use using traditional expression systems, will be expensive and unattractive to vaccine manufacturers who see the vaccine market as economically uninviting. Cost is one of the persistent barriers to deployment of new vaccines to populations that need them most urgently. This factor will inhibit the development and distribution of safe and effective new vaccines against high priority pathogens.