Plant-produced polio vaccines could help eradicate age old disease

August 15, 2017, John Innes Centre
A. VLPs in vitreous iceB. Reconstruction of poliovirus (PV3)C. A central slice through the VLP to show the empty internal surface.D. Resolution of Poliovirus 3 looking at the VP1 protein pocket E. A resolution of the PV3. Credit: John Innes Centre

Plants have been used to produce a new vaccine against poliovirus in what is hoped to be a major step towards global eradication of the disease.

A cross-cutting team of scientists, including Dr Johanna Marsian working in Professor George Lomonossoff's Lab at the John Innes Centre, Norwich, has produced the novel with a method that uses (VLPs) - non-pathogenic mimics of which are grown in plants.

Genes that carry information to produce VLPs are infiltrated into the plant tissues. The host plant then reproduces large quantities of them using its own protein expression mechanisms.

Professor Lomonossoff, from the John Innes Centre said: "This is an incredible collaboration involving plant science, animal virology and structural biology. The question for us now is how to scale it up - we don't want to stop at a lab technique."

VLPs look like viruses but are non-infectious. They have been biologically engineered so they do not contain the nucleic acid that allows viruses to replicate. This means that they mimic the behaviour of the , stimulating the immune system to respond without causing an infection of poliomyelitis.

Laboratory tests demonstrated that the poliovirus mimics provided animals with immunity from the disease paving the way for human vaccines to be produced by plants on a major scale with the input of pharmaceutical industry collaborators.

The breakthrough was made by a consortium funded by the World Health Organisation (WHO) which is seeking to eradicate a disease that has been known since antiquity.

The WHO is seeking alternative vaccines that avoid use of the live virus as part of an international drive to completely eradicate the virus worldwide.

A global scourge up to the middle of the last century, poliovirus has been reduced by 99 per cent since 1988 due to the Global Polio Eradication Initiative led by the WHO. Current polio vaccines, however, require the production of huge quantities of the virus. Using the live virus not only represents a risk of the virus escaping, the use of the live attenuated (weakened) virus, effectively maintains polio in the global population.

VLPs were expressed at the John Innes Centre using Hypertrans® transient plant expression system which had previously been developed there. This successful development not only holds promise for the production of vaccines for polio: it could become a frontline diagnostic resource in producing vaccines against other viral outbreaks.

"The beauty of this system of growing non-pathogenic virus mimics in plants, is that it boosts our ability to scale-up the production of vaccine candidates to combat emerging threats to human health," said Prof Lomonossoff.

In the past 20 years plants have become serious competitors to bacteria, insect cells, yeast or mammalian cells as production systems for pharmaceutical materials. They are cost-effective requiring simple nutrients, water, carbon-dioxide and sunlight for efficient growth and the transient expression system can be adjusted rapidly with low costs.

The work at the John Innes Centre furthered work of scientists at the University of Leeds, who first discovered a way of producing the virus-like particles (VLP) using the Hypertrans® expression system.

Despite successes of plant-based expression to produce VLPs of papilloma and hepatitis B viruses, poliovirus VLPs had previously proved too unstable to make practical vaccines using this technique. A problem is that the genetic material which causes replication of the virus and which is therefore absent from the VLPs, also has a role in holding the particles together.

An empty polio capsid -- non pathogenic mimics of the poliovirus are grown in plants. Credit: Dimond Light Source & Oxford University

However teams from The National Institute for Biological Standards and Control, and the University of Leeds identified mutations within protein coats which enabled the production of VLPs which are sufficiently stable to act as vaccines. Experiments at the University of Oxford showed that these were identical to native poliovirus retaining their shape when warmed, and which are effective in protecting animals against poliovirus.

The team used cryo-electron microscopy at Diamond Light Source's Electron Bio-Imaging Centre (eBIC) to obtain a clear look at the structure of the VLPs. They confirmed the structure and showed that the external features of the particles were identical to those of poliovirus.

Dave Stuart, Director of Life Sciences at Diamond and Professor of Structural Biology at University of Oxford said, "We were inspired by the successful synthetic vaccine for foot-and-mouth disease, also investigated at Diamond as part of UK research collaboration. By using Diamond's visualisation capabilities and the expertise of Oxford University in structural analysis and computer simulation, we were able to visualise something a billion times smaller than a pinhead and further enhance the design atom by atom of the empty shells. Through information gained at Diamond, we also verified that these have essentially the same structure as the native virus to ensure an appropriate immune response."

This collaboration means manufacturing the particles stabilised in plants on a large scale as precursors to vaccines is now much closer to becoming a reality. The results are outlined in the journal Nature communications: Plant-made Polio 3 stabilised VLPs - a candidate synthetic Polio vaccine.

The collaboration includes the John Innes Centre, The National Institute for Biological Standards and Control, Oxford University, University of Leeds, Diamond Light Source, the Henry Wellcome Building for Genomic Medicine.

Background information: Poliovirus: the scourge of summers past

An ancient Egyptian stone engraving provides a clue that the poliovirus has been a disturbing blight on our lives since antiquity. The 3,500-year-old engraving appears show a polio victim, a priest with a withered right leg.

From then the virus was widely feared up until the middle of the last century and the arrival of the first effective vaccines. Polio is now down to a few hundred cases a year world-wide, but these numbers remain steady as the virus is maintained in the environment by the use of the live attenuated vaccine.

"The poliovirus is a very nasty disease and certainly until the 1950s was a real scourge." said Professor George Lomonossoff of the John Innes Centre, based at Norwich Research Park.

"It was known as the summer plague and here in Norwich the main source of it was bathing in the river Yare near Earlham Park."

"Most people had very mild symptoms but some people got paralytic polio and in worst cases couldn't breathe properly and had to be put in an iron lung in order to breathe."

Poliovirus is the causative agent of poliomyelitis which destroys motor neurons in the central nervous system causing paralysis or even death. Transmission is primarily by ingesting infected water.

The Global Polio Eradication Initiative led by the World Health Organisation has resulted in 99 per cent fewer cases in the past 30 years by using two highly effective vaccines: the live attenuated (weakened) vaccine developed by Albert Sabin and the formaldehyde-inactivated or killed virus developed by Jonas Salk.

Production of both vaccines, developed in the 1950s, requires propagation of large quantities of live poliovirus increasing the risk of accidental re-introductions.

Because of this risk, the WHO has intensified its search for cheap and viable alternatives, this breakthrough using the virus-like particles presents an exciting new option. Virus free vaccines will allow polio to be eradicated, they will prevent recurrences without the risks associated with the using the live virus vaccines.

Explore further: Scientists prove new approach to Polio vaccines works

More information: Johanna Marsian et al. Plant-made polio type 3 stabilized VLPs—a candidate synthetic polio vaccine, Nature Communications (2017). DOI: 10.1038/s41467-017-00090-w

Related Stories

Scientists prove new approach to Polio vaccines works

February 1, 2017
Scientists have identified new ways to provide vaccines against polio, which do not require the growth of live virus for their manufacture.

New technique could enable safer production of polio vaccines

January 19, 2017
A new method to produce a stable fragment of poliovirus could enable safer production of vaccines, according to a study published in PLOS Pathogens.

On the brink of eradication: Why polio research matters

April 20, 2017
In the decades since Dr. Jonas Salk developed the first polio vaccine, cases of polio have exponentially declined. Though once widespread epidemic, the highly infectious childhood disease is now close to global eradication. ...

Two polio vaccines may give greater protection against crippling disease

August 21, 2014
(HealthDay)—Using two types of polio vaccines seems to provide stronger protection against the disease and may boost efforts to eradicate polio, a new study shows.

Using cold adaptation to produce safe inactivated polio vaccine candidates

August 24, 2016
Poliomyelitis, or polio, is a debilitating childhood disease caused by poliovirus. It has been eliminated from most parts of the world thanks to the extensive use of polio vaccines. However, there are concerns that current ...

Polio vaccination: Paper highlights final steps to polio eradication

April 2, 2015
April 12th 2015 marks the 60th anniversary of the publication of Jonas Salk's landmark polio vaccine trial results, which confirmed that the first vaccine against polio was safe and effective. A new review, which was published ...

Recommended for you

Female biology – two X chromosomes and ovaries – extends life and protects mice from aging

December 18, 2018
Around the world, women outlive men. This is true in sickness and in health, in war and in peace, even during severe epidemics and famine. In most animal species, females live longer than males.

Sugar targets gut microbe linked to lean and healthy people

December 18, 2018
Sugar can silence a key protein required for colonization by a gut bacterium associated with lean and healthy individuals, according to a new Yale study published the week of Dec. 17 in the journal Proceedings of the National ...

Get a warrant: Researchers demand better DNA protections

December 18, 2018
New laws are required to control access to medical genetic data by law enforcement agencies, an analysis by University of Queensland researchers has found.

Wound care revolution: Put away your rulers and reach for your phone

December 18, 2018
Monitoring a wound is critical, especially in diabetic patients, whose lack of sensation due to nerve damage can lead to infection of a lesion and, ultimately, amputation. Clinicians and healthcare professionals at the McGill ...

Using light to stop itch

December 17, 2018
Itch is easily one of the most annoying sensations. For chronic skin diseases like eczema, it's a major symptom. Although it gives temporary relief, scratching only makes things worse because it can cause skin damage, additional ...

Law professor suggests a way to validate and integrate deep learning medical systems

December 13, 2018
University of Michigan professor W. Nicholson Price, who also has affiliations with Harvard Law School and the University of Copenhagen Faculty of Law, suggests in a Focus piece published in Science Translational Medicine, ...

1 comment

Adjust slider to filter visible comments by rank

Display comments: newest first

Anonym
not rated yet Aug 15, 2017
"Production of both vaccines, developed in the 1950s, requires propagation of large quantities of live poliovirus increasing the risk of accidental re-introductions."

Moreover, with plants they can avoid the public health fiasco that resulted from injecting contaminated serum into hundreds of millions of children in the '50s and '60s. The contaminant was simian virus 40 (SV-40), a carcinogen in the Salk and Sabin vaccines, both of which used (infected) monkey kidneys to culture the polio virus. Very likely today's cancer epidemic among baby boomers is the result of those vaccines. Of course, the vaccine makers dispute this (but got a law passed in 2005, "just in case" I suppose, shielding them from liability lawsuits).

Source: "The Virus and the Vaccine," Bookchin and Schumaker, 2004, St. Martin's Press, NY.



Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.