Pre-existing humoral immunity against seasonal coronaviruses enhances antibody responses on SARS-CoV-2 vaccination

Abstract Background High homology and cross-reactive immune responses between SARS-CoV-2 and seasonal human coronaviruses (HCoVs) have been reported. However, the impact of pre-existing immunity against seasonal HCoVs on SARS-CoV-2 vaccination is undetermined. Methods We conducted a cross-sectional study involving pediatric and adult participants between August 2020 and August 2023. IgG titers against SARS-CoV-2 and seasonal HCoV-229E, -HKU1, -NL63, and -OC43 were quantified by electrochemiluminescent immunoassay. A paired analysis was performed in a subset of participants with samples collected before and after SARS-CoV-2 vaccination. Results N=1,804 participants (median age: 44 years; range: 2-95) were enrolled. IgG titers against HCoV-229E, -HKU1, and -OC43 increased during early childhood. Among SARS-CoV-2-vaccinated participants without prior SARS-CoV-2 infection, anti-spike IgG titers against SARS-CoV-2 positively correlated with titers against HCoV-OC43, -HKU1, and -NL63 (Spearman r=0.40, 0.26, and 0.12; P 0.0001, 0.0001, and 0.0002). In paired analysis, participants with high baseline HCoV-HKU1 and -OC43 IgG titers developed higher post-vaccination anti-SARS-CoV-2 spike IgG responses than those with low baseline titers (geometric mean AU/mL: 111,384 vs. 54,610 and 113,279 vs. 50,099; P=0.03 and 0.015). Multivariable linear regression analyses demonstrated that baseline HCoV-HKU1 and -OC43 IgG titers remained independently associated with post-vaccination anti–SARS-CoV-2 spike IgG levels (β=110,592 and 108,855; 95%CI, 17,922–203,262 and 12,013–205,697; P=0.020 and 0.028). Conclusion Higher baseline immunity to HCoV-HKU1 and -OC43 was associated with stronger SARS-CoV-2 vaccine–induced antibody responses. These findings suggest that pre-existing immunity against seasonal betacoronaviruses may enhance humoral immune response to SARS-CoV-2 vaccination.