SARS‐CoV‐2 Evolution: Immune Dynamics, Omicron Specificity, and Predictive Modeling in Vaccinated Populations

Abstract Host immunity is central to the virus's spread dynamics, which is significantly influenced by vaccination and prior infection experiences. In this work, we analyzed the co‐evolution of SARS‐CoV‐2 mutation, angiotensin‐converting enzyme 2 (ACE2) receptor binding, and neutralizing antibody (NAb) responses across various variants in 822 human and mice vaccinated with different non‐Omicron and Omicron vaccines is analyzed. The link between vaccine efficacy and vaccine type, dosing, and post‐vaccination duration is revealed. The classification of immune protection against non‐Omicron and Omicron variants is co‐evolved with genetic mutations and vaccination. Additionally, a model, the Prevalence Score (P‐Score) is introduced, which surpasses previous algorithm‐based models in predicting the potential prevalence of new variants in vaccinated populations. The hybrid vaccination combining the wild‐type (WT) inactivated vaccine with the Omicron BA.4/5 mRNA vaccine may provide broad protection against both non‐Omicron variants and Omicron variants, albeit with EG.5.1 still posing a risk. In conclusion, these findings enhance understanding of population immunity variations and provide valuable insights for future vaccine development and public health strategies.