Synthetic polio vaccine developed using plants

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A new vaccine for polio has been developed by using plants to reproduce virus-like particles (VLPs). The research, from a consortium funded by the WHO, is considered to be a major step towards the eradication of polio.

The WHO is seeking to develop an alternative vaccine that avoids the use of live viruses. Current strategies using live poliovirus require its production in large amounts – this not only poses the risk of the risk of the virus escaping, but also effectively maintains the virus in the global population

The novel vaccine, reported recently in Nature Communications, constitutes VLPS – non-pathogenic mimics of polio – grown in plants. The particles lack the nucleic acid that allows poliovirus to replicate; therefore they mimic the virus’s behaviour but can’t cause infection.

The researchers produced VLPs using the Hypertrans® transient plant expression system, developed at the John Innes Centre (Norwich, UK). Genes encoding the particles are inserted into plant tissues, allowing the plant to produce VLPs in large quantities using its own cell machinery.

Senior author, George Lomonossoff, (John Innes Centre), stated: “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.”

Prior to this study, VLPs for poliovirus had proved too unstable to produce practical vaccines. This was due to the lack of nucleic acids, which are removed to produce non-pathogenic particles, but in polio actually also play a role in stabilizing the viral particle. In the new research, teams from the National Institute for Biological Standards and Control (Potters bar, UK) and the University of Leeds (UK) identified protein-coat mutations that enabled the production of stable VLPs.

The researchers went on to demonstrate that the newly stabilized, synthetically-produced VLPs provided protective immunity in animal models challenged with the poliovirus, suggesting this technique could be used to produce vaccines on a major scale.

In addition, teams from the Diamond Light Source (Harwell, UK) used cryo-electron microscopy and single-particle reconstruction to carry out structural analysis of the stabilized mutant. They demonstrated that at a 3.6 Å resolution the structure of the VLPs was almost indistinguishable from wild-type poliovirus.

Author, Dave Stuart, Director of Life Sciences at Diamond commented: “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 (UK) 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 has pioneered the manufacturing of VLPs for polio in plants, suggesting that production on a large scale, and a new vaccine, is now closer to becoming a reality. In addition, it could be used to produce other vaccines, including those for emerging viruses.

Lomonossoff concluded: “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.”

Sources: Marsian J, Fox H, Bahar MW et al. Plant-made polio type 3 stabilized VLPs—a candidate synthetic polio vaccine. Nat. Comms. doi:10.1038/s41467-017-00090-w (2017) (Epub); www.eurekalert.org/pub_releases/2017-08/j-ppv081017.php

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