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Diagrammatic illustration of the process of Plant Molecular Farming (PMF). (Figure 1 from Ref. 5 below)

Diagrammatic illustration of the process of Plant Molecular Farming (PMF). (Figure 1 from Ref. 5 below)

Plant-Based Vaccines – A Great Idea

It’s been over 20 years since I introduced students in my plant sciences classes to the idea of using genetically-engineered plants (GMOs) as a source of edible vaccines.

Basically, the idea was that some crop plants could be genetically engineered to
produce vaccines in their edible parts, which could then be eaten when inoculations were needed.

I think it’s safe to say that one of the chief proponents of this idea, since the early 1990’s, has been Dr. Charles Arntzen.

When Dr. Charles Arntzen of Arizona State University visited Thailand in 1992, he was not expecting a moment of scientific “eureka” that would redirect his career. However, after observing a young Thai mother soothing her fussy infant with bits of banana, this plant molecular biologist was struck with an idea that is both startling and ingenious. What if, in addition to quieting her child, the mother could also administer a life-saving vaccine – in the banana?” (from Ref. 1 below)

(By the way, a recent review of plant-made pharmaceuticals by Dr. Arntzen – please see Ref. 2 below – is what prompted this post.)

–> Fast-Forward to 2016 –> Despite the scientific progress (e.g., see Ref. 3) and all the interest and excitement with regard to this idea (e.g., see Ref. 4) that existed nearly 20 years ago, to date, there is no commercially-available plant-based edible vaccine.

Why not?

Reality Bites….The Banana

Brilliant ideas are often tempered, even sometimes crushed, by reality. And such appears to be the case for edible vaccines.

By 2004, the cumulative number of antigens from pathogens of humans and/or animals successfully expressed in GMO plants had reached almost 50 (from Ref. 5 below). But, by then, the limitations of edible vaccines was also becoming evident.

These limitations included the following:

  • Effectiveness of plant-derived oral vaccines – The stability and immunogenicity of orally-delivered antigens from plants appears to be highly variable, often producing unsatisfactory results. Also, a related concern, especially from a regulatory point of view, is how to deliver a specific dose of vaccine.
  • Human risks – Oral ingestion of food containing antigens may elicit an immune tolerance. Also, there may occur adverse allergic reactions to plant-specific compounds in the edible vaccines.
  • Ecological risks – The risks from field-grown GMO plants expressing vaccine components are not fully known. For example, of serious concern is the potential contamination of non-GMO crop plants and/or wild plants by the “escape” from GMO plants of transgenes coding for antigens “into the wild” – typically via pollen.
  • Government approval – The regulatory obstacles to orally-delivered, plant-derived vaccines may, indeed, be insurmountable at the present time.
  • Social resistance to GMOs – The last, but by no means the least, concern is the anti-GMO attitude of many people, especially with regard to the ingestion of GMO crops.

    These problems have undermined interest from the vaccine industry, and unless financial incentives are found, serious work on edible vaccines will be likely be confined to research labs. But, even though much progress been made in research laboratories, the practical applications of edible vaccines in the “real world” may be up against seemingly overwhelming odds.

    In his own words, Dr. Arntzen explains why promoting the idea of edible vaccines was probably a mistake:

    As I have said in recent years that [the term “edible vaccine”] may have attracted attention in the plant biology realm, but it probably has been much more counterproductive in the traditional vaccine industry. I have come to regret coining the term. In my naiveté, I was ignoring the rigorous regulatory requirements that government agencies and the vaccine industry follow to give us today’s highly effective and wonderfully safe vaccines. I still believe that using plant tissue for low-cost delivery of unpurified (or partially purified) antigens, perhaps as a dry powder, is technically feasible for mucosal vaccination. I see progress in this direction for animal vaccines, which is needed.” (from Ref. 2 below)

    Still, There Is Hope Down On The “Pharm”

    Although it’s unlikely that plant-grown “edible vaccines” will ever be used as originally envisioned, the interest in plants as biosynthetic factories for human and livestock pharmaceuticals, including vaccines, is alive and well. (For example, please see Refs. 6 and 7.)

    The West Africa Ebola virus outbreak of 2014-15 is a good example. As described in a previous post, tobacco plants were used to make an Ebola therapeutic called ZMappTM. (See YouTube video below.)

    And, more recently, tobacco plants were again in the news as “anti-malaria drug factories”.

    With the 2012 FDA approval of plant-made pharmaceutical (PMP) Elelyso for human use, the stage is set for other forthcoming PMPs. So, the future looks bright for “pharming” after all.

    Down on the “Pharm” (Some companies producing biologics and vaccines made in GMO plants that are in clinical development.)

    1. Mapp Biopharmaceutical, Inc. – Using tobacco plants to make components of Ebola vaccine ZMappTM.

    2. Medicago – Making vaccines against viruses (e.g., influenza and HIV) using tobacco plants.

    3. Ventria Bioscience – Making human lactoferrin (VEN 100) in rice as treatment against antibiotic-associated diarrhea.

    4. Planet Biotechnology – Using plants to produce treatment of MERS coronavirus infection.

    References

    1. Mandy, R. (2005) “Banana Vaccines: A Conversation with Dr. Charles Arntzen.”, Journal of Young Investigators, published online September 2005. (Full Text)

    2. Arntzen, C. (2015) “Plant-made pharmaceuticals: from ‘Edible Vaccines’ to Ebola therapeutics.” Plant Biotechnology Journal, Vol. 13, pp. 1013-1016; DOI:10.1111/pbi.12460 (Full Text)

    3. Walmsley, A. M. and C. J. Arntzen (2000) “Plants for delivery of edible vaccines.” Current Opinion in Biotechnology, Vol. 11, pp. 126-129. (Abstract)

    4. Langridge, W. H. R. (2000) “Edible Vaccines.”, Scientific American, Vol. 283, pp. 66-71. (Full Text – PDF)

    5. Arntzen, C., S. Plotkin and B. Dodet (2005) “Plant-derived vaccines and antibodies: potential and limitations.” Vaccine, Vol. 23, pp. 1753–1756.

    6. Yao, J., et al. (2015) “Plants as Factories for Human Pharmaceuticals: Applications and Challenges.” International Journal of Molecular Sciences, Vol. 16, pp. 28549-28565; doi:10.3390/ijms161226122 (Full Text)

    7. Liew, P.S. and M. Hair-Bejo (2015) “Farming of Plant-Based Veterinary Vaccines and Their Applications for Disease Prevention in Animals.” Advances in Virology, Vol. 2015, Article ID 936940; doi.org/10.1155/2015/936940 (Full Text)

    YouTube Video – How to grow an Ebola vaccine with a tobacco plant

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