̽��ֱ�� of Cambridge - Sam Wilks

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

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Staying ahead of the game: Pre-empting flu evolution may make for better vaccines

cjb250 — Thu, 20 Nov 2014 19:00:02 +0000

In a study published today in the journal Science, the researchers in the UK, Vietnam, ̽��ֱ��Netherlands and Australia, led by the ̽��ֱ�� of Cambridge, describe how an immunological phenomenon they refer to as a ‘back boost’ suggests that it may be better to pre-emptively vaccinate against likely future strains than to use a strain already circulating in the human population.

Influenza is a notoriously difficult virus against which to vaccinate. There are many different strains circulating – both in human and animal populations – and these strains themselves evolve rapidly. Yet manufacturers, who need to produce around 350 million doses ahead of the annual ‘flu season’, must know which strain to put in the vaccine months in advance – during which time the circulating viruses can evolve again.

Scientists at the World Health Organisation (WHO) meet each February to select which strain to use in vaccine development. Due to the complexity of human immune responses, this is decided largely through analysis of immune responses in ferrets to infer which strain best matches those currently circulating. However, vaccination campaigns for the following winter flu season usually start in October, by which time the virus may have evolved such that the effectiveness of the vaccine match is reduced.

“It’s a real challenge: the WHO selects a strain of flu using the best information available but is faced with the possibility that the virus will evolve before the flu season,” explains Dr Judy Fonville, one of the primary authors on the paper and a member of WHO Collaborating Centre for Modelling, Evolution and Control of Emerging Infectious Diseases at the ̽��ֱ�� of Cambridge. “Even if it does, though, it’s worth remembering that the flu vaccine still offers much greater protection than having no jab. We’re looking for ways to make an important vaccine even more effective.”

According to the WHO, seasonal influenza causes between 3 and 5 million cases of severe illness each year worldwide, up to 500,000 deaths, as well as significant economic impact. Vaccination policies vary per country, but are typically recommended for those at risk of serious complications, such as pregnant women and the elderly. ̽��ֱ��seasonal flu vaccine has been described as one of the most cost-effective measures of disease prevention, and vaccination therefore has a large health economic benefit. Currently 350 million people partake in annual vaccination programmes. Yet there is room for improvement.

After gathering an extensive amount of immunological data, the team modelled the antibody response to vaccination and infection using a newly developed computer-based method to create an individual’s ‘antibody landscape’. This landscape visualises an individual’s distinct immune profile like a three dimensional landscape with mountains in areas of immune memory and valleys in unprotected areas. ̽��ֱ��technique enables a much greater understanding of how our immune system responds to pathogens such as flu that evolve and re-infect us.

A key finding from the work is that upon infection, a response is seen not just to the infecting influenza strain, but to all the strains that an individual has encountered in the past. It is this broad recall of immunity, that they term the ‘back-boost’, that is the basis for the proposed vaccine improvement.

Dr Sam Wilks, one of the primary authors, explains: “Crucially, when the vaccine strain is updated pre-emptively, we see that it still stimulates better protection against future viruses yet this comes at no cost to the protection generated against currently circulating ones.

“Faced with uncertainty about how and when the flu virus might evolve, it’s better to gamble than to be conservative: if you update early, you still stimulate protection against current strains – much worse is if you update too late. Rather than trying to play ‘catch-up’, it’s better to anticipate and prepare for the likely next step of influenza evolution – and there is no penalty for doing it too soon.”

Professor Derek Smith, also from Cambridge, adds why this may lead to improved vaccines in a relatively short timeframe: “ ̽��ֱ��beauty of this approach is that it would not require any change to the current manufacturing process. From the point that the new strain has been selected through to an individual receiving their shot, the steps will be exactly the same. ̽��ֱ��only difference would be greater protection for the recipient.”

̽��ֱ��team is now combining this research with their other work on predicting the way in which the virus will evolve, and plan to combine these two major pieces of work in prospective clinical trials.

̽��ֱ��international collaboration included researchers from: the Erasmus Medical Center, the Netherlands; the Oxford ̽��ֱ�� Clinical Research Unit & Wellcome Trust Major Overseas Programme and the National Institute of Hygiene and Epidemiology, Vietnam; and the WHO Collaborating Centre for Reference and Research on Influenza at the Victorian Infectious Diseases Reference Laboratory in Melbourne. Its principal funders were the Wellcome Trust and the US National Institutes of Health Centers of Excellence for Influenza Research and Surveillance (CEIRS).

Reference
Fonville, JM et al. Antibody landscapes after influenza virus infection or vaccination. Science; 20 Nov 2014

An international team of researchers has shown that it may be possible to improve the effectiveness of the seasonal flu vaccine by ‘pre-empting’ the evolution of the influenza virus.

Faced with uncertainty about how and when the flu virus might evolve, it’s better to gamble than to be conservative

Sam Wilks

Daniel Paquet

Flu Vaccination Grippe (cropped)

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