Ou-Yang, PuPuOu-YangChuang, Ming-KaiMing-KaiChuangJANN-TAY WANGWANG-HUEI SHENGJung, Chiau-JingChiau-JingJungJEAN-SAN CHIA2026-02-252026-02-252026https://scholars.lib.ntu.edu.tw/handle/123456789/735996Background: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) still evolves and spreads worldwide. Mucosal immunity is the first line of defense against SARS-CoV-2 infections. We tested the hypothesis of whether salivary antibodies (sIgA or IgG) induced by common human coronaviruses (HCoVs) have cross-reactivities and neutralizing effects against SARS-CoV-2. Methods: Paired saliva and serum samples were collected from healthy young adults (n = 98) in 1993 and uninfected healthcare workers during the pandemic (n = 79). sIgA and IgG antibodies against SARS-CoV-2 and HCoV-229E were detected, respectively. Results: A moderate to strong positive correlation was found between levels of anti-SARS-CoV-2 and anti-HCoV-229E sIgA and IgG in saliva. Specific anti-S of SARS-CoV-2 IgA were found in 14 % of saliva, whereas neither anti-NP nor anti-S IgG were found in serum collected in the pre-pandemic era. Cross-reactivities of these sustained anti-HCoVs sIgA or IgG were enriched and confirmed by immunoblotting and also exhibited neutralizing activities against SARS-CoV-2 and its variants using Luminex-based assay. Furthermore, the incidence rate ratios of subsequent SARS-CoV-2 infection were significantly lower in the healthcare workers group with high salivary anti-HCoV-229E S1 sIgA. Conclusion: Our findings suggest that salivary anti-HCoV-229E S1 sIgA antibodies with cross-reactivities against SARS-CoV-2 S1 protein may pose protective potential against SARS-CoV-2.enCross-reactive IgA or IgGSalivary anti-coronavirus antibodiesSevere acute respiratory syndrome coronavirus-2journal article10.1016/j.jmii.2025.12.00441486020