How did vaccination shape the global evolutionary trajectory of SARS-CoV-2?

In a recent study posted on bioRxiv* Preprint server, researchers have developed a most likely (ML) model that captures the evolutionary dynamics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in multiple geographic regions.

In addition, they quantified the effects of vaccination and previous infections on the rate of antigenic discontinuous mutations between SARS-CoV-2 mutants.

The study model described the endogenous and antigenic fitness components of SARS-CoV-2 for this analysis. We also combined data from time-resolved sequencing, epidemiological records, and cross-neutralization assays to infer model parameters.

Background

The rapid turnover of the SARS-CoV-2 gene clade, along with new variants showing increased fitness and infectivity, weakened cross-immunity induced by previous infections and vaccinations. It is also worth noting here that the evolutionary effects of antigenic changes between SARS-CoV-2 mutants are time-dependent, as it depends on herd immunity. Therefore, in the past, widespread vaccination has affected the turnover of the influenza virus circulating clade.

In 2021 and 2019, the global number of coronavirus disease (COVID-19) vaccinations reached approximately 4.5 billion. Nevertheless, studies have poorly quantified the impact of these large-scale vaccination campaigns on the global epidemiological and evolutionary dynamics of SARS-CoV-2.

About research

In this study, researchers received over 5 million quality controls from a global initiative to share all influenza data (GISAID) databases to track all circulating clades of SARS-CoV-2. Obtained the SARS-CoV-2 sequence. They used a set of amino acid (AA) changes to assign gene clades to the obtained sequence data. They then estimated the time-dependent clade frequency from strain counts for about 30 days.

In the last two years, three SARS-CoV-2 variants (VOCs) and their associated clades have become widespread worldwide: i) Alpha (α) ii) between March and June 2021. Between June and December 2021 Delta (δ) iii) Omicron (o) in 2022. Researchers have tracked the frequency of VOC shifts in multiple countries and three US states that meet unified standards: New York, Texas, and California. They made sure that all the data was accurate and time-resolved. One showed a clade that circulates before α, including those with an early 614G mutation in wild-type (wt) and SARS-CoV-2 spike (S) proteins.

The study analysis included 11 regions for the 1-α shift, 16 regions for the α-δ shift, and 14 regions for the δ-o shift. Finally, the team analyzed the region for both α-δ and δ-o shifts to track the long-term evolutionary trajectory of SARS-CoV-2.

Survey results

In 2021, primary vaccination had a global impact on the rate of SARS-CoV-2 clade shift, booster vaccination elicited higher cross-protection, but the antigenic choice was weak. .. Therefore, the findings highlight the importance of incorporating evolutionary feedback into vaccine design.

In addition, research analysis revealed that antigen selection increased in intensity and broadened its target. For example, infection-induced antigen selection increased in intensity from 0.01 to 0.03 with α–δ and δ–o shifts. Both vaccination and previous infections induced substantial antigen selection in the circulating SARS-CoV-2 mutant, regulating the pace of subsequent clade shifts.

However, antigen selection did not cause or prevent these shifts, as the inherent functional changes produced sufficient compatibility benefits for invading mutants, regardless of herd immunity.

In other words, SARS-CoV-2 first produced multiple antigenic components (different mutants) during the spillover of zoonotic diseases to humans. When SARS-CoV-2 transitions to an endemic state, herd immunity to its circulating mutant promotes its antigen evolution, but this transition slows its antigen evolution. Also, most of the essential changes in SARS-CoV-2 antigenic drift are compensatory, as observed in the SARS-CoV-2 evolutionary pathway leading to the emergence of omicrons. Interestingly, in Omicron, the stronger binding affinity for human cell receptors compensates for the attenuated fusion.

Conclusion

The data-driven fitness model used in the study facilitated tracking of the ongoing multifaceted antigen evolution of SARS-CoV-2. You can also predict how SARS-CoV-2 will evolve in the future and inform preemptive immunization strategies. More importantly, research analysis showed that the relationship between vaccination rate and rate of evolution was complex due to the correlation between cross-immune channels. As a result, less vaccination increases SARS-CoV-2 infection and builds cross-immunity through other immune channels.

It is also worth noting that infection-inducing antigen selection always contains the opposite type of component. Therefore, primary infection with the ancestral SARS-CoV-2 clade produced a positive selection, whereas infection with a new clade so created produced a negative selection. This cycle extended the coexistence of both ancestral clades and invading clades. SARS-CoV-2 antigen selection produced a complex but measurable time-dependent pattern.

*Important Notices

bioRxiv publishes unpeer-reviewed preliminary scientific reports and should not be considered definitive, guide clinical / health-related behaviors, or be treated as established information.