The Power of Plants

Vaccines made in plants? The concept may sound a little outlandish, but the basic principle is simple: to produce vaccines and other pharmaceutical proteins in food crops such as tomatoes, potatoes or bananas. Studies have shown that eating these vaccine-producing plants can elicit a mucosal immune response. One of the key driving forces behind the research and development of plant-made vaccines is the lack of access to medicines (both financially and geographically) of much of the world’s rural poor. While the Western world takes the control of infectious diseases for granted, cholera, rotavirus, malaria, and many others continue to be major killers of children under five in developing countries.

As a result, much effort has gone into the generation of novel vaccine production platforms with the potential to address the needs of the world’s poor. Vaccines generated in plants are inexpensive to produce, easy to scale up and can be maintained at room temperature for prolonged periods of time. Plants also eliminate the risk of contamination by human pathogens, yet can undergo post-translational modifications similar to their conventionally produced vaccine counterparts. Plant-made vaccines originated among a few research groups at a handful of universities across the globe, but they are now becoming a reality. The first plant-made vaccine to undergo human clinical trials was designed to protect against Hepatitis B virus. This vaccine was initially generated in transgenic potato tubers, which were then fed (raw) to individual volunteers. The researchers found a marked increase in antibody titer against the virus in patients who ate the transgenic potatoes – and demonstrated the first proof-of-concept that vaccines generated and delivered in this fashion could elicit a strong mucosal immune response (1).

Since then, a number of pharmaceuticals have been produced for oral delivery using transgenic plant technologies. Most noteworthy is the glucocerebrosidase (GCD) enzyme for treatment of Gaucher disease. An Israeli company, Protalix, is able to produce GCD at a fraction of the cost of its conventionally made counterpart, using carrot suspension cells. Vaccines and pharmaceuticals have also been produced from expression vectors based upon plant viruses. Recombinant plant viruses are able to rapidly generate high yields of pharmaceutical proteins, whilst circumventing public concern over genetically modified plants. The Canadian company Medicago, for example, has used a plant virus to express pandemic influenza virus vaccine rapidly and in large quantities. Other plant viruses have been used to generate microbicides to HIV, and even a personalized vaccine to non-Hodgkin lymphoma.

The recent Ebola epidemic in West Africa brought plant virus expression vectors to the forefront once again. Two monoclonal antibodies developed by Mapp Biopharmaceuticals have been generated using a tobacco plant-based production system and have been administered to several patients with Ebola (2).
Plant viruses have also found a role in cancer medicine – as vehicles for tumor homing and immunotherapy. When injected into a cancer patient, empty plant virus-like particles have been shown to navigate and accumulate within solid tumors. Once lodged within these tumors, the virus is able to elicit a highly localized immune response, which blocks tumor progression. This appears to be accomplished by activating quiescent neutrophils, which in turn secrete cytokines and stimulate T-lymphocytes to attack the tumor cells. Nontoxic and biodegradable, these plant viruses could act alone or in conjunction with a payload carried on the surface, or within the virus particle itself, to eliminate and prevent the recurrence of several cancers (3). Over the past decade, I believe that plants will continue to gain momentum as a novel platform for pharmaceutical production. The fact that the vast majority of patents are held by universities or publicly funded research institutes makes for an accessible intellectual property landscape. And new developments, such as the use of plant viruses to block solid tumor progression, are confirming plant-based pharmaceuticals as “one to watch” in the coming years.

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