Immune Responses to SARS-CoV-2 Variants WT and XBB.1.9: Assessing Vulnerabilities and Preparedness

Objectives: The emergence of SARS-CoV-2 variants with enhanced immune evasion capabilities poses ongoing challenges for maintaining population-level immunity. This study aim to evaluate neutralizing antibody responses to the wild-type (WT) strain and the Omicron sublineage XBB.1.9 in the Israeli population using serum samples collected between August 2022 and January 2023, prior to widespread circulation of XBB.1.9. Methods: Pseudovirus-based microneutralization assays incorporating variant-specific spike proteins were employed to measure neutralizing geometric mean titers (GMTs) across subgroups categorized by age, gender, socioeconomic status, and geographic region. Results: Neutralizing titers against XBB.1.9 were significantly lower than those against WT across all demographic groups, with a 29-fold reduction in neutralization activity against XBB.1.9, underscoring the immune escape potential of XBB.1.9. For WT, older adults (≥65 years) exhibited higher titers than younger individuals (p < 0.01), whereas no significant age-related differences were observed for XBB.1.9 (p > 0.05). Regional disparities in WT immunity were identified, with higher titers in Northern Israel compared to Jerusalem and Southern regions. By contrast, XBB.1.9 neutralization showed no significant regional variation. Conclusions: These findings demonstrate substantially reduced neutralization of XBB.1.9 compared to WT and reveal disparities in WT immunity by age and region. The results emphasize the need for updated vaccines targeting immune-evasive variants and for tailored vaccination strategies to address regional and demographic gaps in protection.