Preexisting Humoral Immunity Against Seasonal Coronaviruses Enhances Antibody Responses on SARS-CoV-2 Vaccination

High homology and cross-reactive immune responses have been reported between SARS-CoV-2 and seasonal human coronaviruses (HCoVs). However, the impact of preexisting immunity against seasonal HCoVs on SARS-CoV-2 vaccination is undetermined.

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.

A total of 1804 participants were enrolled (median age, 44 years; range, 2-95). IgG titers against HCoV-229E, -HKU1, and -OC43 increased during early childhood. Among participants without prior SARS-CoV-2 infection who were SARS-CoV-2-vaccinated, 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, respectively; P < .0001, P < .0001, and P = .0002). In paired analysis, participants with high baseline HCoV-HKU1 and -OC43 IgG titers developed higher postvaccination anti-SARS-CoV-2 spike IgG responses than those with low baseline titers (geometric mean [arbitrary units/mL]: 111 384 vs 54 610 and 113 279 vs 50 099; P = .03 and .015). Multivariable linear regression analyses demonstrated that baseline HCoV-HKU1 and -OC43 IgG titers remained independently associated with postvaccination 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 = .020 and .028).

Higher baseline immunity to HCoV-HKU1 and -OC43 was associated with stronger SARS-CoV-2 vaccine-induced antibody responses. These findings suggest that preexisting immunity against seasonal betacoronaviruses may enhance humoral immune response to SARS-CoV-2 vaccination.