Threat... and opportunity

The coronavirus epidemic, Co­vid-2019 has, so far, claimed over 2,300 lives and infected over 75,000 persons. So far, nothing has stopped its spread. One positive outcome of the crisis may be a review of vaccine research and development processes, leading to much faster development and deployment of new vaccines.

On average, it takes over 10 years for a new vaccine to move from the lab onto pharmacy shelves. This involves a process of preclinical development; three clinical phases; preregistration; registration; and launch. There are hopes that new technology, fast-tracked clinical trials and fast regulatory clearances could shorten this to just 12-18 months, in the case of Covid-2019.

Viruses are tiny pieces of RNA or DNA (not both, unlike normal cells) that invade the cells of hosts (humans, animals, birds) in order to replicate. They come in all sorts of shapes. Coronaviruses like Covid-2019 are RNA-based.

Covid-2019 uses coiled spikes of protein to attach itself to a cell. After the spike is attached to the cell, it uncoils and drills a hole in the cell to enter. The virus then fools the body into believing that it is giving legitimate genetic instructions, in order to replicate.

The body combats viruses by recognising the characteristic shape of a virus and developing antibodies to attack anything, which is that shape. Antibodies can work even if the body recognises only part of the characteristic virus shape. Viruses in turn, tend to mutate, changing shape to evade immune responses.

Vaccines work by getting the body to recognise the virus, and thus, helping trigger antibodies. Hence, a vaccine must contain at least part of a virus. Sub-unit vaccines do contain just part of a virus — sub-units are commonly used for flu shots and hepatitis B. There are also attenuated vaccines, which contain a weakened version of a live virus (the measles vaccine is an attenuated vaccine) and inactivated vaccines, which contain a dead virus (such as rabies).  

In 2017, the Coalition for Epidemic Preparedness Innovations (CEPI) was launched in Davos. CEPI is a public-private international body headquartered in Norway. It was an international response to the emergence of deadly viruses such as SARS, Ebola, Zika etc. The CEPI’s mission is to fast track vaccine development and ensure widespread access to vaccines.

The CEPI is now working in coordination with WHO to promote development of new vaccines against Covid-19. This includes programmes with pharmaceutical companies like Inovio, CureVac and Moderna Inc and also research programmes with the University of Queensland and the US National Institute of Allergy and Infectious Diseases. The CEPI will try to push promising vaccines into clinical testing quickly, with a target of going from gene sequencing of the virus, to clinical testing, inside just 16 weeks.

Research at the University of Queensland could be a crucial component. A team there has pioneered a new technique, called Molecular Clamping. Instead of using a live sample of the virus, modern genetic sequencing allows the genetic code to be studied directly.

The Covid-2019 gene sequence was published by China on January 11. The Queensland team zeroed in on the code for the “spike”, which they can reproduce without generating the whole virus. Cryo-electron microscopy was used to map the spike in 3D. This is also a new technology for using electron microscopes in cold chambers to decipher biomolecules — the 2017 Nobel for Chemistry was awarded for this.

The approach: Find an effective vaccine that recognises the coiled spike, before it penetrates cells and does damage. The spike tends to uncoil if it is separated from the main body of the virus and this makes it hard to recognise the coiled shape.

This is where molecular clamping comes into play. Molecular clamping uses small clamps of protein to keep the spikes fixed in their coiled shape. It was developed about seven years ago by University of Queensland scientists, Keith Chappell, Daniel Watterson and Paul Young.

Last week, the University team announced they had managed to clamp out shapes and they were hoping to start clinical trials on animals within a week. This involves making large batches of clamped shapes, and using this to manufacture potential vaccines by inserting into animals. If this works, the potential vaccines will go into clinical trials on humans. A successful vaccine may be developed using these methods. However, the CEPI reckons it’s statistically likely that it will take about 21 tries at creating such test vaccines before a vaccine that works on humans is developed. After that, there’s hopes that the crisis would lead to speedy registration and regulatory clearances, followed by mass manufacture. If this process works, the next time a new virus emerges, there could be an even faster response.

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