In a recent study published on the bioRxiv* preprint server, researchers developed a maximum likelihood (ML) model to capture the evolutionary dynamics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) across multiple geographic regions.
In addition, they quantified the impact of vaccination and previous infection on the rate of antigenic changes between SARS-CoV-2 variants.
Study: Vaccination shapes the evolutionary trajectories of SARS-CoV-2. Image credit: Tong_stocker/Shutterstock
The study model took into account the intrinsic and antigenic fitness components of SARS-CoV-2 for this analysis. In addition, he combined time-resolved sequencing data, epidemiological records, and cross-neutralization assays to infer model parameters.
background
The rapid turnover of SARS-CoV-2 genetic clades, with new variants showing increased fitness and transmissibility, attenuated cross-immunity induced by previous infections and vaccinations. It is also worth noting here that, as it depends on population immunity, the evolutionary impact of antigenic changes between SARS-CoV-2 variants is time-dependent. Thus, in the past, widespread vaccinations influenced the turnover of circulating influenza virus clades.
In 2021, the global count of vaccines against coronavirus disease 2019 (COVID-19) reached approximately 4.5 billion. However, studies barely quantified the impact of these large-scale vaccination campaigns on the global epidemiological and evolutionary dynamics of SARS-CoV-2.
About the study
In the present study, researchers obtained more than five million quality-controlled SARS-CoV-2 sequences from the Global Initiative to Share All Influenza Databases (GISAID) to track all circulating clades of SARS-CoV-2. They used a set of amino acid (AA) changes to assign genetic clades to the obtained sequencing data. They subsequently inferred time-dependent clade frequencies from strain counts over about 30 days.
In the last two years, three variants of concern (VOCs) of SARS-CoV-2 and their associated clades reached global prevalence: i) Alpha (α) between March and June 2021, ii) Delta (δ) between June and December 2021, and iii) Omicron (o) in 2022. The researchers recorded the frequency trajectories of VOC changes for several countries meeting the uniform criteria and three US states, namely New York, Texas and California. They ensured that all data was accurate and time resolved. One denoted clades circulating before α, including wild type (wt) and those with the early 614G mutation in the SARS-CoV-2 spike protein (S).
The study analysis included 11 regions for the 1 – α shift, 16 for the α – δ shift, and 14 for the δ – o shift. Finally, the team analyzed the regions for both α−δ and δ−o changes to track the long-term evolutionary trajectories of SARS-CoV-2.
Results of the study
In 2021, while primary vaccination affected the rate of SARS-CoV-2 clade shifts globally, booster vaccination induced higher cross-protection but weaker selection for antigenic escape. Therefore, the study results highlight the importance of incorporating evolutionary feedback into vaccine design.
Furthermore, analysis of the study revealed that antigenic selection increased in strength and broadened its target. For example, infection-induced antigenic selection increased in strength from 0.01 to 0.03 in α-δ and δ-o changes. Both vaccination and previous infections induced substantial antigenic selection in circulating SARS-CoV-2 variants and modulated the rate of subsequent clade shifts.
However, antigenic selection neither caused nor prevented these changes because the inherent functional changes generated sufficient fitness advantage for the invading variants, regardless of population immunity.
In other words, SARS-CoV-2 generated multiple antigenic components (different variants) initially, that is, during its zoonotic spillover to humans. If SARS-CoV-2 transitions to an endemic state, population immunity to its circulating variants will fuel its antigenic evolution, but this transition will slow down its antigenic evolution. Furthermore, most of the intrinsic changes in the antigenic drift of SARS-CoV-2 will become compensatory, as observed during the evolutionary path of SARS-CoV-2 leading to the emergence of Omicron. Interestingly, in Omicron, stronger binding affinity to human cell receptors compensates for the attenuated fusogenicity.
Conclusions
The data-driven fitness model used by the study facilitated tracking the ongoing multifaceted antigenic evolution of SARS-CoV-2. It could also predict how SARS-CoV-2 will evolve in the future to inform preventive vaccination strategies. More importantly, the study’s analysis showed that the relationship between vaccination coverage and rate of evolution was complex due to correlations between channels of cross-immunity. Consequently, fewer vaccines lead to more SARS-CoV-2 infections, generating cross-immunity in other channels of immunity.
It should also be noted that antigenic selection induced by infection always contains components of opposite types. Therefore, while primary infections by the ancestral SARS-CoV-2 clade generated positive selection, infection by newly created clades generated negative selection. This cycle prolonged the coexistence of both ancestral and invading clades. SARS-CoV-2 antigenic selection produced complex but measurable time-dependent patterns.
*Important news
bioRxiv publishes preliminary scientific reports that are not peer-reviewed and therefore should not be considered conclusive, guide clinical practice/health-related behavior, or be treated as established information.