Plant Produced Polio Vaccines Could Make Global Polio Eradication A Reality

Highlights:

• Commercial production of polio vaccine requires large quantities of the live virus which are then modified for vaccine purposes

• Accidental release of this virus could lead to polio outbreaks or the vaccine itself could cause infection in a child with lowered immunity

• Harmless virus like particle (VLP) grown in plants can help eradicate polio without risk of infection and recurrences associated with live polio virus

Virus like particles (VLPs) mass produced from plants give the WHO led initiative of global eradication of polio a major shot in the arm; the icing on the cake is that the VLPs are non-pathogenic and there is thus no risk of accidental release and other risks associated with live polio vaccines. The plant derived VLPs were developed by the joint efforts of a group of scientists across many centers and fields including Dr Johanna Marsian working in Professor George Lomonossoff’s Lab at the John Innes Centre, Norwich, teams at the University of Leeds and the Diamond Light Source’s Electron Bio-Imaging Centre (eBIC) at the University of Oxford. The results appear in the journal Nature communications titled “Plant-made Polio 3 stabilised VLPs - a candidate synthetic Polio vaccine”.

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."

Production of Polio VLP Prototype In The Lab – Overcoming Initial Hiccups 

• Though prior research teams have produced VLPs of papilloma and hepatitis B viruses, creation of polio virus VLPs remained a challenge as removal of the genetic material to create the VLP caused them to become unstable and thus unsuitable for mass vaccine production

• However, scientists from The National Institute for Biological Standards and Control, and the University of Leeds identified mechanisms which allowed the formation of
• VLPs which remain sufficiently stable to act as vaccines.

• Further tests at Oxford University confirmed that these VLPs remained stable and retained their shape and stability when heated, similar to live virus.

• The VLPs resemble viruses but are non-infectious. They have been modified so they do not contain the nucleic acid genetic material that enables viruses to multiply. They do however contain viral surface proteins organized in a manner similar to native viruses. They can therefore stimulate immunity without causing disease.

• Using cryo-electron microscopy at Diamond Light Source’s Electron Bio-Imaging Centre (eBIC), the Leeds team obtained a clear view of the structure of the VLPs and confirmed that the external features of the particles were similar to that of the poliovirus.

Expression of VLPs From Plants For Vaccine Production

• Once the VLPs were successfully engineered in the lab from native virus, the next step was the task of mass producing these particles on a large scale using plant sources for vaccines.

• To this end, genes that contain information to produce VLPs are introduced into the plant tissues.

• The host plant then produces huge quantities of VLPs using its protein expression systems through technology developed by Prof. Lomonossoff at the John Innes Centre - the Hypertrans® expression system.

• The entire process from the introduction of genes for the VLP into the plant tissues and harvesting the VLPs from the crushed leaves happens in a matter of weeks.

"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.

Plant Based Vaccine Production – The Way To Go In Future?

In the last two decades, plant based mechanisms have emerged as attractive options for the production of commercial pharmaceutical materials. They pose serious competition to bacteria, yeast cells, insect and mammalian cells due to several benefits.

Their advantages include cost effectiveness requiring simple and easily available nutrients for growth namely water, carbon dioxide and sunlight. Their transient expression system can also be easily modified at a low cost.

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Cost Effective VLP Expression System – The Hypertrans System
The Hypertrans gene expression system permits concomitant production of multiple gene products in a regulated fashion within plant tissues. Using this system, several new products can be cheaply and rapidly developed, validated, scaled and produced.

Potential applications of the technology include:

• Generation of complex proteins, such as enzymes and antibodies for research purposes.
• Production of virus-like particles for vaccine development or nano-technology.
• Generation of complex biochemicals that are difficult or impossible to synthesize
• artificially or those that occur only in trace amounts in nature.

About Poliomyelitis – In Brief

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Polio or infantile paralysis is an infectious disease caused by the polio virus and transmitted by ingesting contaminated water. In children with normal immunity, it is a subclinical illness without any overt symptoms. In some cases it presents as a self-limiting flu like illness without paralysis. In a small proportion of cases however, the virus causes paralysis which is often permanent. There is no cure and prevention is by immunization.

There are two highly effective vaccines namely the Sabin vaccine, a live attenuated vaccine administered orally and the Salk vaccine, a killed vaccine given as an intramuscular injection. Currently 99 percent infection has been eradicated worldwide, with some stray cases being reported from the developing world.

In conclusion, the plant derived vaccine makes the WHO quest to eradicate polio a distinct possibility in the near future, without the incidental risks associated with live vaccines.

Reference:

1. Johanna Marsian et al. Plant-made polio type 3 stabilized VLPs—a candidate synthetic polio vaccine, Nature Communications (2017).
2. Poliomyelitis (polio) - (http://www.who.int/topics/poliomyelitis/en/)

Source-Medindia