Contributions of the international plant science community to the fight against infectious diseases in humans-part 2: Affordable drugs in edible plants for endemic and re-emerging diseases

Abstract

The fight against infectious diseases often focuses on epidemics and pandemics, which demand urgent resources and command attention from the health authorities and media. However, the vast majority of deaths caused by infectious diseases occur in endemic zones, particularly in developing countries, placing a disproportionate burden on underfunded health systems and often requiring international interventions. The provision of vaccines and other biologics is hampered not only by the high cost and limited scalability of traditional manufacturing platforms based on microbial and animal cells, but also by challenges caused by distribution and storage, particularly in regions without a complete cold chain. In this review article, we consider the potential of molecular farming to address the challenges of endemic and re-emerging diseases, focusing on edible plants for the development of oral drugs. Key recent developments in this field include successful clinical trials based on orally delivered dried leaves of Artemisia annua against malarial parasite strains resistant to artemisinin combination therapy, the ability to produce clinical-grade protein drugs in leaves to treat infectious diseases and the long-term storage of protein drugs in dried leaves at ambient temperatures. Recent FDA approval of the first orally delivered protein drug encapsulated in plant cells to treat peanut allergy has opened the door for the development of affordable oral drugs that can be manufactured and distributed in remote areas without cold storage infrastructure and that eliminate the need for expensive purification steps and sterile delivery by injection.

Keywords: endemic disease; molecular farming; oral delivery; plant-made pharmaceuticals; re-emerging disease.

Figure 1

Mechanism of oral drug delivery and examples of chloroplast therapeutics and booster vaccines. (a) The cGMP growing facility for lettuce leaf biomass production. (b) The lyophilizer that dehydrates lettuce biomass through optimized programming for freeze‐drying. (c) Optimized grinding to maintain the intactness of plant cells. (d) The capsule/gum preparation maintaining antigen stability. (e) The oral delivery of proteins bioencapsulated in plant cells. (f) Mechanism of immune suppression/tolerance or conferring immunity. GM1 ganglioside receptors on intestinal epithelial cells facilitate uptake CTB‐fused proteins. DCs are antigen‐presenting cells, induce antigen‐specific T and B cells. The IFN‐γ and Th2 cytokines (IL‐4, IL‐10) are critical for cell‐mediated and humoral immunity. After TGF‐β production, FoxP3⁺ T_reg cells are induced by DCs. The immune tolerance via induction and maintenance of FoxP3⁺ T_reg cells is mediated by TGF‐β. (g) Examples of potential chloroplast‐derived booster vaccines against viral (polio, COVID‐19) and bacterial (anthrax, cholera, tuberculosis) diseases. (h) Oral tolerance induction and immune suppression in haemophilia and the prevention of peanut allergy.