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The hunt for a COVID-19 vaccine

The COVID-19 pandemic has affected millions of people worldwide, creating a global health emergency. Researchers all over the world are racing to understand SARS-CoV-2, the coronavirus behind the disease, and find a safe and effective vaccine. At least two UK research groups have developed candidates that will soon enter clinical trials, but there is still plenty of work to do to protect the world’s health.


The search for a vaccine

On 31 December 2019, health authorities in Wuhan, China, reported a cluster of patients with cases of pneumonia with an unknown cause to the WHO. The disease was eventually named COVID-19 and a novel coronavirus, SARS-CoV-2, identified as the virus behind it.

The virus rapidly spread, infecting millions worldwide in a matter of months. Many countries have introduced restrictive measures such as social distancing or lockdowns to contain or slow the spread, protect vulnerable populations and avoid overburdening healthcare services. Despite these efforts, protecting the population through widespread vaccination will be the only way to beat the disease in the long term.

By the end of March 2020 there were already more than 40 vaccine candidates in development from academic groups, established pharmaceutical companies and start-ups in many countries. This number had grown to at least 70 by the middle of April as more organisations joined the international research effort. Some are created from genetic material (RNA or DNA) derived from SARS-CoV-2, while others are based on fragments of its proteins.

A small number of vaccines are close to or have already started early-stage clinical trials where they are being evaluated for safety and effectiveness in small groups of volunteers. Ultimately, only one vaccine needs to succeed but having a wide field of potential candidates increases the chances that one or more will work.

The international research community has responded to COVID-19 at unprecedented speed. There has been incredible global cooperation - Dr John Tregoning, Imperial College London

Similar experimental vaccines have already been tested in early stage clinical trials against MERS (Middle East Respiratory Syndrome), proving that this technique is safe for use in humans. Clinical trials of the virus-based SARS-CoV-2 vaccine are starting in April 2020. At Imperial College London, Professor Robin Shattock and his team are working on a more experimental ‘plug and play’ approach, creating a vaccine made from self-amplifying RNA encapsulated in tiny droplets. This vaccine contains genetic instructions encoding both the virus spike protein (the part most likely to induce an immune response) and RNA copying machinery, enabling the vaccine to self-replicate inside cells and generate a greater protective immune response. The Imperial team expects to start clinical trials in June 2020.

When will the coronavirus vaccines be ready?

All of the vaccines in development must first prove they are safe and effective in small-scale clinical trials, which could take many months. Next come the challenges of scaling-up manufacturing and larger clinical trials involving hundreds or thousands of people before widespread rollout. This will be no small feat: vaccines are commercially risky investments for pharmaceutical companies and production facilities are generally designed to produce one specific vaccine. The scaling up of infrastructure to manufacture any new vaccine will be a very serious challenge.

A global vaccine is still unlikely before 2021, but we could see large-scale trials late in 2020 - Dr John Tregoning, Imperial College London

There are still many questions about COVID-19 that need to be answered as we progress towards effective vaccine implementation: How long does immunity last and how many doses will be needed? Does protection vary between people according to genetic background, age or sex? And who should get priority access to vaccination in order to most effectively protect vulnerable populations?

Learning from this pandemic to prepare for the next

The response from the research community to COVID-19 has been impressive, but it has also highlighted that the world needs to be better prepared for the next pandemic, whatever it may be. There is an urgent need to support and fund global capabilities in immunology, modelling, diagnostics and vaccination against all infectious diseases - including the ones we don’t even know about yet.

Typically, when infectious diseases fade from the headlines, the funding for research dries up too. If intensive research into coronavirus infections like SARS and MERS had continued in the wake of past outbreaks, we might have been better equipped for tackling COVID-19 today.

It is also essential not to overlook the impact that the pandemic will have on progress against the many other infectious diseases that still cause death and misery around the world. The disruption to healthcare infrastructure that currently delivers routine immunisation programmes for lethal childhood diseases like polio, typhoid and measles risks the lives of many thousands of children.


CASE STUDY

New technology on trial

Professor Robin Shattock and his team at Imperial College London are building a ‘plug and play’ vaccine development platform, with the aim of rapidly producing novel RNA vaccines against emerging diseases based on their genetic code. The COVID-19 pandemic is the first real test of this technology, and progress has been incredibly fast.

“We were able to go from having the virus’ genetic code to building a prototype vaccine and our first animal experiments within three weeks. In animals, the vaccine induced very potent neutralizing antibodies with a single immunisation,” says Shattock.

Crucially, the Imperial team’s RNA-based vaccine amplifies itself in the body, giving it a unique advantage over other candidates when it comes to manufacturing. “We can use very low doses of RNA in the self-amplifying vaccine, so we can make a million doses in a litre of reaction material,” he explains.

Shattock thinks the simplicity of this genetic platform approach, combined with relatively easy scale-up and manufacturing, will play a central role in providing vaccines for existing diseases and future outbreaks. “We could build networked vaccine manufacturing platforms around the world. So if another pandemic occurs, everyone could make a vaccine for their local population, instead of waiting for centralized production. We’re not there yet, but that is the vision.”​


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