More than a year and half since the first known case of COVID-19, the virus that causes this disease (SARS-CoV-2) continues to evolve; the virus gradually accumulates many small changes in it’s genomic sequence over time.?
While most of these changes to the virus will have minor effects on the properties of the virus, occasionally a set of changes will result in a variant that poses increased risk to the population. Specific variants of concern (e.g., the delta variant) have already emerged that spread more rapidly and even lead to more severe disease. The ability of the virus to “find” such variants of concern depends on its ability to change over time.
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In our recent study, we investigated how mass vaccination limits the ability of the virus to freely change, potentially preventing future and more dangerous variants.?
We have investigated this using a combination of globally collected SARS-CoV-2 genomic sequences (~1.8 million sequences via the GISAID initiative) and SARS-CoV-2 genomic sequences from vaccinated and unvaccinated patients at the Mayo Clinic Health System.?
We like to think of the evolving viral sequence as a tree (akin to a family tree), with the first SARS-CoV-2 sequence that infected a human patient as the tree’s root. Over time, this tree has grown and ‘split’ many times into distinct branches (distinct genomic variants of the virus).?
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In our study, we have quantified the virus’ sequence diversity using a metric called “lineage entropy”, essentially telling us how many branches the viral sequence tree has. We found that the virus’ sequence diversity was constantly increasing, up until the start of mass vaccination in December 2020.?
After the commencement of mass vaccination, we suddenly saw that the virus sequence diversity was decreasing (i.e., the tree is losing branches). This is a sign of evolutionary pressure on the virus, meaning the virus is now limited in how it can change and still infect individuals.?
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When we look at individual countries, we observe a direct relation between the percentage of the population that is vaccinated and the diversity of the viral sequences observed.?
As more of the population in a country gets vaccinated, the local diversity of viral sequences is decreased. This trend held true in 26 out of 27 countries included in our study.
To understand how vaccination can reduce the diversity in changes to the SARS-CoV-2 virus, we looked specifically at which variants survived mass vaccination. We found increased changes to antigenic sites, the parts of the virus that are recognized as a part of vaccine-induced immune protection, with about four times as many changes in known antigenic sites than other parts of the viral genome.?
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This could be because viral variants that had few changes in their antigenic sites are no longer viable in a post-vaccine environment. It is important to understand that these variants with changes in their antigenic sites already existed before mass vaccination, they are not created as a response to vaccination.
Comparing SARS-CoV-2 genomic sequences obtained from SARS-CoV-2 positive individuals at the Mayo Clinic Health System, we found that most of these individuals harbor the same variant of SARS-CoV-2 (the locally predominant alpha-variant). However, there were small changes to the viral sequence obtained from each SARS-CoV-2 infected individual.?
Viral sequences from unvaccinated individuals had about twice as many unique changes than those from vaccinated individuals, further supporting our conclusion that vaccination reduces the ability of the virus to explore sequence changes and find new, potentially dangerous, variants.
Our study presents the first evidence that COVID-19 vaccines are fundamentally restricting the evolutionary pathways accessible to SARS-CoV-2, limiting the virus’ ability to mutate.?
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The societal benefit of mass vaccination may go far beyond the widely reported mitigation of SARS-CoV-2 infection risk and amelioration of community transmission, as this evidence suggests that it may also include protection against rampant viral evolution.
About the author: Venky Soundararajan is the Founder & Chief Scientific Officer at nference Labs, which has built the world’s leading pharmacological and diagnostic insights and decision support platform developed by applying the latest artificial intelligence (especially deep learning) techniques to massive real world clinical data. Views expressed in this article are the author's alone.