Previous Infections and Vaccination Affect COVID-19 Mutation Vulnerability

The immune response of a person to variants of SARS-CoV-2, the virus that causes COVID-19, is affected by past exposure to infections, and variances in the emphasis of immune responses may help scientists learn how to optimize vaccines in the future to give wide protection.

According to a new study, persons differ in their susceptibility to distinct mutations in emerging SARS-CoV-2 variants based on the earlier infections.

This is due to the fact that the version of SARS-CoV-2 to which a person was first exposed impacts how well their immune system responds to different components of the virus and how well they are protected against other variants.

“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

The result highlights the need of ongoing surveillance programs for detecting the emergence of novel variations and understanding variances in SARS-CoV-2 immunity throughout the community.

It will also be crucial for future vaccination methods, which must take into account both the viral variant contained in the vaccine and how the immune responses of the population may differ in 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 University 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.”

The study, which was published today in the journal Science, involves ten research institutes, including the University of Cambridge, and created a comprehensive snapshot of early worldwide population immunity to COVID-19.

Researchers obtained 207 serum samples (extracted from blood samples) from persons who had either been spontaneously infected with one of the numerous previously circulating SARS-CoV-2 variants or who had been vaccinated against SARS-CoV-2 with varying numbers of doses of the Moderna vaccine.

They then looked at the immunity that these people had established and discovered that there were significant changes in immune responses depending on which version 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 University 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.”

The researchers employed a technique known as ‘antigenic cartography’ to compare the similarities of different SARS-CoV-2 viral strains. This test determines how efficiently human antibodies generated in response to one virus infection respond to infection with a variation of that virus. It determines whether the virus has evolved sufficiently to evade the human immune response and cause disease.

The generated ‘antigenic map’ depicts the link between a wide range of previously distributed SARS-CoV-2 variants. Omicron variations differ substantially from one another, which helps to explain why many patients died from Omicron infections despite immunization or previous infections with a different version.

Immunity to COVID-19 can be obtained through infection with SARS-CoV-2 or immunization. Vaccines provide protection against disease and its effects. They function by stimulating the immune system, helping it to recognize and respond quickly to SARS-CoV-2 exposure, preventing sickness. However, the SARS-CoV-2 virus, like other viruses, continues to mutate in order to evade human immunity.

The main SARS-CoV-2 virus in circulation during the first year of the epidemic was the B.1 type. Since then, several variations have evolved that have evaded pre-existing immunity, producing reinfections in persons who have previously had COVID.

“The 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.

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