̽��ֱ�� of Cambridge - Centre for Pathogen Evolution

Vulnerability to different COVID-19 mutations depends on previous infections and vaccination, study suggests

jg533 — Fri, 06 Oct 2023 08:00:00 +0000

A new study has found that people differ in how vulnerable they are to different mutations in emerging variants of SARS-CoV-2.

This is because the variant of SARS-CoV-2 a person was first exposed to determines how well their immune system responds to different parts of the virus, and how protected they are against other variants.

It also means that the same COVID-19 vaccine might work differently for different people, depending on which variants of SARS-CoV-2 they have previously been exposed to and where their immune response has focused.

̽��ֱ��discovery underlies the importance of continuing surveillance programmes to detect the emergence of new variants, and to understand differences in immunity to SARS-CoV-2 across the population.

It will also be important for future vaccination strategies, which must consider both the virus variant a vaccine contains and how immune responses of the population may differ in their response to it.

“It was a surprise how much of a difference we saw in the focus of immune responses of different people to SARS-CoV-2. Their immune responses appear to target different specific regions of the virus, depending on which variant their body had encountered first,” said Dr Samuel Wilks at the ̽��ֱ�� of Cambridge’s Centre for Pathogen Evolution in the Department of Zoology, first author of the report.

He added: “Our results mean that if the virus mutates in a specific region, some people’s immune system will not recognize the virus as well - so it could make them ill, while others may still have good protection against it.”

̽��ֱ��research, published today in the journal Science, involved a large-scale collaboration across ten research institutes including the ̽��ֱ�� of Cambridge and produced a comprehensive snapshot of early global population immunity to COVID-19.

Researchers collected 207 serum samples - extracted from blood samples - from people who had either been infected naturally with one of the many previously circulating SARS-CoV-2 variants, or who had been vaccinated against SARS-CoV-2 with different numbers of doses of the Moderna vaccine.

They then analysed the immunity these people had developed, and found significant differences between immune responses depending on which variant a person had been infected with first.

“These results give us a deep understanding of how we might optimise the design of COVID-19 booster vaccines in the future,” said Professor Derek Smith, Director of the ̽��ֱ�� of Cambridge’s Centre for Pathogen Evolution in the Department of Zoology, senior author of the report.

He added: “We want to know the key virus variants to use in vaccines to best protect people in the future.”

̽��ֱ��research used a technique called ‘antigenic cartography’ to compare the similarity of different variants of the SARS-CoV-2 virus. This measures how well human antibodies, formed in response to infection with one virus, respond to infection with a variant of that virus. It shows whether the virus has changed enough to escape the human immune response and cause disease.

̽��ֱ��resulting ‘antigenic map’ shows the relationship between a wide selection of SARS-CoV-2 variants that have previously circulated. Omicron variants are noticeably different from the others – which helps to explain why many people still succumbed to infection with Omicron despite vaccination or previous infection with a different variant.

Immunity to COVID-19 can be acquired by having been infected with SARS-CoV-2 or by vaccination. Vaccines provide immunity without the risk from the disease or its complications. They work by activating the immune system so it will recognise and respond rapidly to exposure to SARS-CoV-2 and prevent it causing illness. But, like other viruses, the SARS-CoV-2 virus keeps mutating to try and escape human immunity.

During the first year of the pandemic, the main SARS-CoV-2 virus in circulation was the B.1 variant. Since then, multiple variants emerged that escaped pre-existing immunity, causing reinfections in people who had already had COVID.

“ ̽��ֱ��study was an opportunity to really see - from the first exposure to SARS-CoV-2 onwards - what the basis of people’s immunity is, and how this differs across the population,” said Wilks.

This research was funded by the National Institute of Allergy and Infectious Diseases and National Institutes of Health.

Reference

Wilks, S H et al: ‘Mapping SARS-CoV-2 antigenic relationships and serological responses.’ Science, October 2023. DOI: 10.1126/science.adj0070

10 October 2023: New projects to kickstart future vaccine development awarded UKRI funding

̽��ֱ�� ̽��ֱ�� has been awarded £3.46 million by the UKRI as part of a consortium project, PROVAC: Evolutionarily smart vaccine strain selection for proactive vaccinology.

This project aims to enhance the SARS-CoV-2 vaccine strain selection process to provide the best possible protection for the UK population. It will predict which variants may emerge in the future and measure immune responses against this potential future evolution. This will enable researchers to choose the variant of the virus to use in the next vaccine.

Continual monitoring and updating of the variant is necessary to protect those at high-risk of complications from COVID-19, who will require further vaccinations against the evolving virus.

Professor Derek Smith at the ̽��ֱ�� of Cambridge’s Centre for Pathogen Evolution/ Department of Zoology will lead the consortium, which also involves researchers at Imperial College London, Francis Crick Institute, ̽��ֱ�� College London Hospitals, and the ̽��ֱ�� of Glasgow. ̽��ֱ��consortium is the direct result of the researchers’ substantial involvement in multiple aspects of the UK COVID-19 response.

̽��ֱ��award is made as part of UKRI’s five-year strategy Transforming Tomorrow Together 2022 to 2027 to harness the full power of the UK’s research and innovation system to tackle large-scale, complex challenges. In total £25m has been awarded to new projects to tackle epidemics and disease mutation.

Read UKRI's full award announcement here.

This page was originally published on 6 October 2023 and last updated: 10 October 2023.

A person’s immune response to variants of SARS-CoV-2, the virus that causes COVID-19, depends on their previous exposure – and differences in the focus of immune responses will help scientists understand how to optimise vaccines in the future to provide broad protection.

It was a surprise how much of a difference we saw in the focus of immune responses of different people to SARS-CoV-2.

Sam Wilks

Alexandra Koch on Pixabay

Virus variants

̽��ֱ��text in this work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Images, including our videos, are Copyright © ̽��ֱ�� of Cambridge and licensors/contributors as identified. All rights reserved. We make our image and video content available in a number of ways – as here, on our main website under its Terms and conditions, and on a range of channels including social media that permit your use and sharing of our content under their respective Terms.

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Vikings had smallpox and may have helped spread the world’s deadliest virus

Anonymous — Thu, 23 Jul 2020 18:30:46 +0000

Smallpox spread from person to person via infectious droplets, killed around a third of sufferers and left another third permanently scarred or blind. Around 300 million people died from it in the 20th century alone before it was officially eradicated in 1980 through a global vaccination effort – the first human disease to be wiped out.

Now an international team of scientists have sequenced the genomes of newly discovered strains of the killer virus after it was extracted from the teeth of Viking skeletons from sites across northern Europe. ̽��ֱ��findings are published today in the journal Science.

“We already knew Vikings were moving around Europe and beyond, and we now know they had smallpox. Just as people travelling around the world today quickly spread COVID-19, it is likely Vikings spread smallpox. Only back then, they travelled by ship rather than plane,” said Professor Eske Willerslev in the ̽��ֱ�� of Cambridge’s Department of Zoology and St. John’s College, and Director of ̽��ֱ��Lundbeck Foundation GeoGenetics Centre at the ̽��ֱ�� of Copenhagen, who led the study.

̽��ֱ��team found smallpox - caused by the variola virus - in 11 Viking-era burial sites in Denmark, Norway, Russia, and the UK. They also found it in multiple human remains from Öland, an island off the east coast of Sweden with a long history of trade.

They were able to reconstruct near-complete variola virus genomes for four of the samples. ̽��ֱ��genetic structure of this earliest-known smallpox strain is different to the modern smallpox virus eradicated in the 20th century.

“There are multiple ways viruses may diverge and mutate into milder or more dangerous strains. This is a significant insight into the steps the variola virus took in the course of its evolution,” said Dr Barbara Mühlemann, formerly at the Centre for Pathogen Evolution at the ̽��ֱ�� of Cambridge, now based at the Institute of Virology at Charité – Universitätsmedizin Berlin, and one of the first authors of the report.

Historians believe smallpox may have existed since 10,000 BC but until now there was no scientific proof that the virus was present before the 17th century. It is not known how it first infected humans but, like COVID-19, it is believed to be a zoonotic disease - one that originated in an animal.

Smallpox was eradicated throughout most of Europe and the United States by the beginning of the 20th century but remained endemic throughout Africa, Asia, and South America. ̽��ֱ��World Health Organisation launched an eradication programme in 1967 that included contact tracing and mass communication campaigns - all public health techniques that countries have been using to control today’s coronavirus pandemic. But it was the global roll-out of a vaccine that ultimately enabled scientists to stop smallpox in its tracks.

While it is not clear whether these ancient strains of smallpox were fatal, the Vikings must have died with smallpox in their bloodstream for the scientists to detect it up to 1400 years later. It is also highly probable there were epidemics earlier than these findings.

“While written accounts of disease are often ambiguous, our findings push the date of the confirmed existence of smallpox back by a thousand years,” said Dr Terry Jones at the Centre for Pathogen Evolution at the ̽��ֱ�� of Cambridge and the Institute of Virology at Charité – Universitätsmedizin Berlin, and one of the senior authors who led the study.

He added: “To find smallpox so genetically different in Vikings is truly remarkable. No one expected that these smallpox strains existed. It has long been believed that smallpox was in Western and Southern Europe regularly by 600 AD, around the beginning of our samples. We have proved that smallpox was also widespread in Northern Europe. Returning crusaders or other later events have been thought to have first brought smallpox to Europe, but such theories cannot be correct.”

“Smallpox was eradicated, but another strain could spill over from the animal reservoir tomorrow. What we know in 2020 about viruses and pathogens that affect humans today is just a small snapshot of what has plagued humans historically,” said Willerslev.

This research is part of a long-term project sequencing 5000 ancient human genomes and their associated pathogens. It was made possible thanks to a scientific collaboration between ̽��ֱ��Lundbeck Foundation, ̽��ֱ��Wellcome Trust, ̽��ֱ��Nordic Foundation, and Illumina Inc.

Reference

Muhlemann, B. et al. 'Diverse variola virus (smallpox) strains were widespread in northern Europe in the Viking Age. Science, July 2020. DOI: 10.1126/science.aaw8977

Adapted from a press release by St John’s College, Cambridge.

Scientists have discovered extinct strains of smallpox in the teeth of Viking skeletons – proving for the first time that the killer disease plagued humanity for at least 1400 years.

Just as people travelling around the world today quickly spread COVID-19, it is likely Vikings spread smallpox. Only back then, they travelled by ship rather than plane.

Eske Willerslev

Thames Valley Archaeological Services

Massacred 10th century Vikings found in a mass grave at St John’s College, Oxford

̽��ֱ��text in this work is licensed under a Creative Commons Attribution 4.0 International License. Images, including our videos, are Copyright © ̽��ֱ�� of Cambridge and licensors/contributors as identified. All rights reserved. We make our image and video content available in a number of ways – as here, on our main website under its Terms and conditions, and on a range of channels including social media that permit your use and sharing of our content under their respective Terms.

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