GM plants grow polio vaccines

October 2017

World-wide, polio is now a disease of the past in all but two countries. The battle has been waged with mass vaccination programmes reaching, for example, 95% of infants in Europe. Even in Pakistan and Afghanistan, polio's last stand, the annual incidence has been reducing dramatically year-on-year and is down to a few tens of cases. Indeed, conquering this virus has been one of the great success stories of modern medicine.

The current vaccine is produced from a slow process of growing live polio in chicken eggs, after which the virus particles are extracted, killed and preserved, commonly by freezing, until needed. Apart from the time involved, cost and storage practicalities, it's not unusual for these vaccines be harmful: some individuals are sensitive to eggs, and because the 'killed' viruses sometimes aren't actually dead the vaccine can cause an outbreak of the disease it's supposed to prevent. The incidences of polio from the latter source far outnumber the remaining wild-type cases.

Accordingly, the World Health Organisation (WHO) has awarded a $1.5 million grant to researchers developing promising new techniques for producing safer vaccines.

Efforts have focused on generating 'virus-like particles' (VLPs). These consist of the outer protein structure of the polio virus, which is what the immune system encounters and reacts to, but lack the inner genetic material which is what invades the victim's cells and causes disease.

All the techniques being trialled involve GMOs to produce the virus-like particles. Candidates are GM yeast and GM cultured insect cells, both of which have been used successfully in the past for VLP vaccine production. A third candidate is a fast-growing GM plant related to tobacco. No major plant-based vaccine has yet been widely introduced.

Plants can be very prolific generators of VLP with yields of up to 3 grams of protein per kilogram of leaf biomass. However, development has lagged behind other systems because the notion of 'edible vaccines' in GM fruit and vegetables to save the developing world was an early pro-GM PR stunt: these were never a reality because fruit and vegetables are too variable to satisfy the precision demanded for successful vaccination, but the fixation on the idea stymied alternative research.

Belatedly, an English team is finally thinking outside the box and has created a plant-generated polio vaccine which has proved effective against the virus in laboratory animals. Their next challenge is to see whether it works as hoped in clinical trials.

The scientists are excited about the potential of their GM tobacco-like plants, which don't court the controversy surrounding a GM food plant, to serve the vaccine industry. No doubt the vaccine industry is also excited because such a vast source of quick and easy vaccine will be very lucrative, and, if it works, polio will only be the first of many.

OUR COMMENT

It's excellent news that safer and more practical vaccines against devastating viral diseases are being developed. What's disturbing is the attention paid to the GM plant alternative.

Polio is an animal-infecting virus. The best 'fake' will be produced by animal cells with an animal physiology, which is why insect-cell human VLP generation has been successful.

Isolating plants grown on a commercial scale from environmental influences is difficult. Cells cultured in closely-controlled conditions have a better potential for producing a reliable, uniform, clinically acceptable product. However, it's the GM plants which are hitting the headlines, almost to the exclusion of the cell-based methods.

The John Innes Center, England's major GM crop research unit, reported its promising WHO-funded vaccine research in June 2016. Over a year later, the research became BBC 'news', although the only difference in the two reports seems to be that the vaccine from a GM plant was pronounced "cheap".

Media accounts of how the new vaccine is produced describe plants which are 'hijacked', and materials for vaccine production which are 'created', 'combined', 'put into' and finally 'takes hold' in the plant. The words 'GM', 'genetic modification', or 'genetic transformation' don't feature anywhere in either report. This is a strange omission because the technique clearly involves engineering artificial DNA coding for the viral proteins, adding further artificial DNA to give it the appropriate qualities for plant-virus infection, plus very likely yet further artificial DNA to give it the appropriate bacterial qualities needed for intermediate production stages in bacteria. This DNA construct is used to genetically transform "soil" bacteria which also happen to be plant pathogens. The resulting GM bacteria are used to infect plant cells which they genetically transform to produce viral proteins.

The description of the ease with which the GM viral protein is harvested seems almost offhand: "Infected leaves were mixed with water, blended, and the polio vaccine was extracted". 'Extracted' is not a straightforward, nor risk-free process: all plant cell debris and plant enzymes which could interfere with the final product have to be completely removed, and the GM protein concentrated down to a pure form. Before being signed off for use, each batch will have to demonstrate that no novel changes or proteins have crept in.

All this doesn't really look quite as "low tech", or "surprisingly easy" a solution to polio vaccine production as is made out.

Any mention of drugs growing in fields raises concerns about interactions with the environment. In this case, there's the delightful prospect of the 'empty' viral protein regaining pathogenic viral DNA from who knows where in the field and causing the biggest (but novel) epidemic we've ever witnessed.

Zika virus is mentioned in the BBC report as another much-needed and highly topical use for the GM tobacco-like plant system. It should be noted, however, that virus-like particles "closely resembling Zika viruses" and found to be a highly effective vaccination in mouse tests, have recently been produced from monkey-cell cultures.

Unlike GM foods, these vaccines are designed for administration in measured, isolated, recorded doses, and will undergo clinical testing. This means that any negative effects due to the multiple GM and plant-like qualities of the final vaccine should come to light. It will be interesting to note if these polio-busting plants emerge as a winner and become PR-friendly 'proof' of the benefits of GM crops, or if they vanish quietly under the carpet because they've proved embarrassingly risky.

Meanwhile, Pakistan has launched its first nationwide polio vaccination drive, which aims to reach more than 37 million children under five in four days. The GM plant vaccine might already have missed this particular boat.

SOURCES:

• World Bites, Metro 19.09.17
• Michelle Morales, Progress Toward Polio Eradication - Worldwide, 2015-2016, Center for Disease Control, 13.05.16
• Plant-based vaccine among front runners in search for new polio jab, John Innes Centre News and Events, 10.06.16
• James Gallagher, Plants 'hijacked' to make polio vaccine, BBC News 17.08.17
• Andris Zeltins, 2013, Construction and Characterization of Virus-Like Particles: A Review, Molecular Biotechnology
• Hélène Boigard, et al., 2017, Zika virus-like particle (VLP) based vaccine, PLoS

Photo: Conventional tobacco plants growing in Virginia, United States. Source Creative Commons