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

Area of Science:

• Virology
• Immunology
• Epidemiology

Background:

• Host immunity, vaccination, and prior infection significantly influence SARS-CoV-2 spread dynamics.
• The co-evolution of viral mutations, ACE2 receptor binding, and neutralizing antibody responses is critical for understanding variant impact.

Purpose of the Study:

• To analyze the co-evolution of SARS-CoV-2 mutations, ACE2 binding, and neutralizing antibody responses in vaccinated humans and mice.
• To reveal the relationship between vaccine efficacy, type, dosage, duration, and immune protection against different variants.
• To introduce a novel model, the Prevalence Score (P-Score), for predicting variant prevalence in vaccinated populations.

Main Methods:

• Analysis of SARS-CoV-2 mutation, ACE2 binding, and neutralizing antibody (NAb) responses.
• Evaluation of vaccine efficacy across different types, dosages, and post-vaccination durations in 822 human and mouse subjects.
• Development and validation of the Prevalence Score (P-Score) model.

Main Results:

• Immune protection against non-Omicron and Omicron variants co-evolved with genetic mutations and vaccination status.
• Hybrid vaccination (wild-type inactivated + Omicron BA.4/5 mRNA) demonstrated potential broad protection, though EG.5.1 remains a risk.
• The P-Score model showed superior predictive capability for new variant prevalence in vaccinated individuals compared to existing models.

Conclusions:

• Findings enhance understanding of population immunity variations in response to SARS-CoV-2 vaccination and infection.
• Insights support the development of more effective future vaccines and refined public health strategies.
• Hybrid vaccination strategies may offer broader protection, but continuous surveillance for emerging variants is essential.