Vaccination against COVID-19 could stem the evolution of “more suitable” variants of SARS-CoV-2 – .

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Vaccination against COVID-19 could stem the evolution of “more suitable” variants of SARS-CoV-2 – .


Researchers in the United States and India presented the first known evidence that the rollout of the 2019 coronavirus disease (COVID-19) vaccination restricts the evolving and immune pathways accessible to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

Venky Soundararajan of nference Labs, Cambridge, Mass., And colleagues have found that the diversity of SARS-CoV-2 lineages is declining nationally as mass vaccination rates against COVID-19 increase.

The researchers also found that compared to unvaccinated COVID-19 patients, vaccinated individuals who developed a breakthrough infection with SARS-CoV-2 harbored viruses with significantly lower diversity in the B cell epitopes that are exploited. after vaccination.

“This study demonstrates that mass vaccination may constitute an antigenic obstacle to the evolution of more capable and transmissive variants of SARS-CoV-2, highlighting the urgent need to stem vaccine reluctance as a key step towards mitigate the global burden of COVID-19, ”the team writes.

A pre-printed version of the research paper is available on the site medRxiv* server, while the article is subject to peer review.

Understanding the evolution of SARS-CoV-2 is imperative to fight the pandemic

The host immune response following infection with SARS-CoV-2 is a key selection pressure that influences the emergence of new viral strains.

“Understanding longitudinal trends in the evolution of SARS-CoV-2 and mapping the mutational landscape of the antigen is imperative to comprehensively address the current pandemic and future epidemics,” says Soundararajan and colleagues.

The rapid development of COVID-19 vaccines and the massive roll-out of vaccination in many countries have enabled more than 800 million people to be now fully immunized worldwide.

Such accelerated immunization of a large part of the population at the height of the current pandemic could significantly increase the evolutionary pressure on the SARS-CoV-2 virus, the researchers warn.

“However, to date, there has been no comprehensive study on the impact of global immunization efforts on the course of SARS-CoV-2,” they write.

The availability of globally shared data offers a ‘timely opportunity’

Since the start of the COVID-19 epidemic in late December 2019, global data sharing efforts have resulted in the deposit of more than 1.8 million SARS-CoV-2 genomes from 183 countries and territories in the database. data from the Global Avian Influenza Data Sharing Initiative (GISAID). by May 2021.

“The availability of genomic and immunological data provides a timely opportunity to systematically characterize the antigenic mutational landscape of SARS-CoV-2,” says Soundararajan and colleagues.

What did the researchers do?

Researchers conducted a longitudinal analysis of SARS-CoV-2 genomes available in the GISAID database to capture patterns of viral evolution associated with vaccination. They also performed viral genome sequencing for 23 patients vaccinated with breakthrough COVID-19 and 30 unvaccinated COVID-19 patients.

Analysis of the 1.8 million SARS-CoV-2 genomes revealed a total of 1,296 different viral lines.

SARS-CoV-2 genomes show a global decline in sequence diversity coinciding with mass vaccination against COVID-19. (a) Schematic overview of the estimation of genomic diversity of SARS-CoV-2 (bc) Diversity of SARS-CoV-2 lines in GISAID data, quantified using the entropy of the probability distribution of the lineage in one month time windows. Vertical dotted lines indicate when countries have achieved immunization coverage of 1% of their total population. (d) Scatter plot showing the correlation between the country-level percentage of fully vaccinated individuals (after OWID21) and the entropy of the SARS-CoV-2 lineage. (e) Distribution of the Pearson correlation coefficient between the country-level percentage of fully vaccinated individuals and the entropy of the SARS-CoV-2 lineage for the 25 countries with more than 25% of their population fully vaccinated (at June 26, 2021) and at least 4 months with 100 or more sequences submitted to GISAID, after the start of vaccination. The ISO 3166-1 alpha-3 code of the countries included and their Pearson correlation are listed in the legend of the figure.

Surprisingly, the team found that the diversity of these lineages has declined globally, with this decline appearing to coincide with the start of the rollout of mass vaccination.

When researchers analyzed the relationship between vaccination rates and lineage entropy in 25 countries where more than 25% of the population was fully vaccinated, they found that the decline in lineage diversity was indeed correlated with increasing mass vaccination rates.

Additionally, the decline in lineage diversity was associated with an increased dominance of the variants of concern B.1.1.7 (alpha), B.1.1.617 (delta) and P.1 (gamma), suggesting that these variants could be “Fitter” SARS-CoV-2 lines.

B cell epitopes had a higher mutational load than T cell epitopes

Since COVID-19 vaccines exploit B and T cell epitopes, the team analyzed the prevalence of mutations in each known epitope residue.

This revealed a higher mutational load in neutralizing B cell epitopes than in neutralizing T cell epitopes.

In addition, the variants of concern contained more mutations in the B cell epitopes than the non-variants of concern.

The team says the results suggest that the SARS-CoV-2 spike protein is currently under high B-cell-induced selection pressure, with worrisome variants showing the most significant increases in cell epitope mutations. B.

The viral spike protein is the main structure that SARS-CoV-2 uses to infect host cells and the main site harboring emerging mutations that confer the increased transmissibility and immune evasion that have been observed for some variants.

Indeed, genomic sequencing of the SARS-CoV-2 genomes of COVID-19 patients revealed that unvaccinated individuals shared significantly more mutational similarities of B cell epitopes with variants of concern than vaccinated patients who developed a revolutionary infection.

What did the authors conclude?

“This study presents the first known evidence that COVID-19 vaccines fundamentally restrict the evolutionary and antigenic pathways accessible to SARS-CoV-2,” explains Soundararajan and colleagues.

The researchers say that although the analysis did not directly predict variant neoepitopes, it highlights the importance of epitopes that are mutated recurrently during viral evolution in response to immune pressure.

“The societal benefit of mass vaccination may therefore go well beyond the widely reported mitigation of the risk of SARS-CoV-2 infection and improvement of community transmission, to include the containment of the galloping viral evolution ”, they conclude.

*Important Notice

medRxiv publishes preliminary scientific reports that are not peer reviewed and, therefore, should not be considered conclusive, guide clinical practice / health-related behavior, or treated as established information.

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