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Against Breast Cancer researchers revealing the coronavirus camouflage, aiding the hunt for a vaccine

Professor Max Crispin

As the country adjusts to life during the Coronavirus pandemic, with public acts of appreciation for the men and women of the NHS and the hundreds of thousands who have selflessly joined the volunteer Army, we may just be witnessing the beginning of a lasting legacy to the current healthcare crisis.

In research laboratories around the world scientists have been joining the battle against the virus by lending their expertise to bring help to the most vulnerable members of society. Against Breast Cancer’s lead researcher at the University of Southampton, Professor Max Crispin and his world class team are using their knowledge of glycobiology to discover how the virus manages to evade the immune system, this knowledge could help to pave the way for the development of a vaccine.

Coronavirus vaccine research

Research led by the University of Southampton has revealed the fundamental features of the SARS-CoV-2 coronavirus that causes COVID19. The researchers have produced the first model of a spike of the virus which shows how it disguises itself to enter human cells undetected, and the viral proteins which are the target of antibodies and vaccine research. The findings of this study could provide crucial information to help scientists currently searching for a vaccine.

The SARS-CoV-2 virus has a large number of spikes sticking out of its surface which it uses to attach to and enter cells in the human body. These spikes are coated in sugars, known as glycans, which disguise their viral proteins and help them evade the body’s immune system.

The research team, led by Professor Max Crispin, studied the structure of the glycans covering the surface of a mimetic of a viral spike using equipment previously purchased through a grant from the Bill and Melinda Gates Foundation through the Collaboration for AIDS Vaccine Discovery.

They were then able to map the structure of the glycans which provides important information about how accessible the viral protein surface is to antibodies, this is an important step in vaccine design.

"By coating themselves in sugars, viruses are like a wolf in sheep’s clothing, but one of the key findings of our study is that despite how many sugars there are, this coronavirus is not as highly shielded as some other viruses."

Professor Max Crispin

Viruses like HIV, which hang around in one host, have to evade the immune system constantly and they have a really dense coat of glycans as a shield to the immune system; but in the case of the coronavirus the lower shielding by sugars attached to it may reflect that it is a ‘hit and run’ virus, moving from one person to the next. However, the lower glycan density means there are fewer obstacles for the immune system to neutralise the virus with antibodies. So this is a very encouraging message for vaccine development.

At Southampton, Professor Crispin’s team includes PhD students Yasunori Watanabe and Joel Allen, and they worked closely with Jason McLellan’s team from the University of Texas who were the first to determine the structure of SARS-CoV-2. They have released their findings ahead of peer-review on the BioRxiv preprint server.

Professor Crispin’s team has a very strong history in analysing the glycans of viruses and they have made key discoveries determining the features of the natively folded spike of HIV.

They are now working with partners who have developed candidate vaccines, including Prof. Rogier Sanders at the University of Amsterdam, and are now analysing the glycan content in Southampton. Evaluating the glycans on immunogens will determine how closely they mimic a natively folded viral spike and will help understand the immune response to vaccine candidates.

Professor Crispin’s laboratory is currently funded by the Bill and Melinda Gates Foundation through the Collaboration for AIDS Vaccine Discovery, the International AIDS Vaccine Initiative, the European AIDS Vaccine Initiative, the Scripps Consortium for HIV/AIDS Vaccine Development and Against Breast Cancer.

Coronavirus represents the greatest challenge we have ever faced. We are lending all the support and expertise we can to help overcome this crisis and to assist those vulnerable members of society most at risk.

Richard Bahu, Chair of Trustees
In addition to group’s work supporting the vaccine efforts, our PhD student Hannah Smith, funded by Cisco, has volunteered to assist in the virus testing at the Southampton General Hospital during this critical phase of the pandemic.

We recognise sharing resources and expertise is crucial to overcoming the current health crisis and the impact Coronavirus has made on our ability to raise the vital funds we need to continue our research into secondary spread is unprecedented.

Our current best estimates forecast a 50% drop in income, so in order to protect funding for our research projects difficult decisions have already been taken. We understand challenging research requires long term support, our primary focus is on maintaining our commitment to these projects, and the incredibly talented people working on them, in some of the UK’s most respected research institutions.

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Against Breast Cancer

Against Breast Cancer is a charity dedicated to funding ground-breaking research to increase survival after a breast cancer diagnosis by focusing on secondary spread, the cause of all breast-cancer related deaths. We fund research that addresses critical gaps in scientific resources and knowledge to help doctors diagnose and treat secondary breast cancer faster and more effectively, and to understand factors that may increase or reduce the risk of secondary spread so that people can make informed diet and lifestyle choices.

We have directly funded the collection of,and continue to fund the storage of over 23,000 blood and urine samples, provided annually by over 3,300 women with breast cancer from 56 hospitals across the UK in our Diet & Lifestyle Study, the largest national study of its kind. Researchers can determine differences between women who develop secondary breast cancer and those who do not by studying this collection of biological samples and dietary and lifestyle information provided at the same time.

Contact details:

Robert Fleming, Head of Development

T: 07928 423348

E.mail: rob@againstbreastcancer.org.uk

Website: www.againstbreastcancer.org.uk

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