- 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
Virus like particles (VLPs)
- Harmless virus like particle (VLP) grown in plants can help
eradicate polio without risk of infection and recurrences associated with
live polio virus
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
The plant derived VLPs were
developed by the joint efforts of a group of scientists across many centers and
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
titled "Plant-made Polio 3 stabilised VLPs - a candidate
synthetic Polio vaccine".
‘Novel virus like particles (VLPs) grown from plants are non-pathogenic and could become a major source of vaccine production against polio and other viruses as well.’
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
- However, scientists
from The National Institute for Biological Standards and Control, and the
University of Leeds identified
mechanisms which allowed the
- 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
Expression of VLPs From
Plants For Vaccine Production
- 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.
- 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.
Plant Based Vaccine Production - The Way To Go In
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
Cost Effective VLP Expression System - The Hypertrans
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:
About Poliomyelitis - In
- 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.
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
namely the Sabin vaccine, a
vaccine administered orally and the Salk vaccine, a killed vaccine
given as an intramuscular injection.
Currently 99 percent infection has been
worldwide, with some stray cases being reported from the
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.
- Johanna Marsian et al. Plant-made polio type 3 stabilized VLPs—a candidate synthetic polio vaccine, Nature Communications (2017).
- Poliomyelitis (polio) - (http://www.who.int/topics/poliomyelitis/en/)