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

The emergence of SARS-CoV-2 variants with enhanced immune evasion capabilities continues to challenge efforts to sustain population-level immunity. Among these, the XBB lineage, particularly the XBB.1.9 sub-variant, has garnered attention due to extensive spike protein mutations that reduce recognition by neutralizing antibodies. In this study, we evaluated neutralizing antibody titers against both the SARS-CoV-2 wild-type (WT) strain and the XBB.1.9 variant using serum samples collected from the Israeli population between August 2022 and January 2023, prior to widespread XBB.1.9 circulation.Our analysis revealed significantly reduced neutralizing titers against XBB.1.9 compared to WT across all demographic groups (p < 0.0001), underscoring its pronounced immune escape potential. For the WT strain, older individuals (≥ 65 years) exhibited higher titers (p < 0.0023), likely reflecting increased vaccine and booster uptake; however, this age-related difference was not observed for XBB.1.9 (p > 0.05), indicating diminished protection across age groups. Regional disparities in WT titers, higher in Northern Israel than in Jerusalem and Southern regions, suggest differential vaccine access and healthcare infrastructure, yet no such variation was seen for XBB.1.9.These findings highlight critical gaps in immunity against XBB.1.9, especially in populations historically underserved by vaccination efforts. The results underscore the urgent need for updated vaccines tailored to immune-evasive variants and for culturally sensitive outreach strategies to improve vaccine equity. Further studies should evaluate the efficacy of XBB-specific vaccines and the durability of immune protection to inform long-term strategies for SARS-CoV-2 control.