Figure 5. Antibody responses are directed against the S2 subunit of the HCoV-OC43 spike protein.

(A) Fold change in responses to various domains/subunits in the HCoV-OC43 spike protein and nucleocapsid. Indirect ELISAs were used to analyze responses to the NTD, S1 subunit and S2 subunit of the HCoV-OC43 spike protein, in addition to the HCoV-OC43 nucleocapsid. Fold change via ELISA was determined relative to the average value in the SARS-CoV-2 antibody-negative blood donor cohort as indicated by the gray division in the figure. Antibody levels are increased against all antigens apart from the nucleocapsid, with the largest increase in antibody response to the S2 subunit of the spike protein. (B) Correlation in responses between SARS-CoV-2 antigens and HCoV-OC43 spike protein domains and nucleocapsid. The log-scale OD₄₀₅ values from the HCoV-OC43 spike and nucleocapsid ELISAs (along the rows) is compared to the MSD V-PLEX SARS-CoV-2 results (columns). A linear model fit on the log-scale is annotated with the associated 95% confidence intervals and R² and P values. Values and model fits for the nonfatal COVID-19 outcomes group are given in purple, while red is used for the fatal outcome group. The HCoV-OC43 S2 subunit ELISA result is only correlated with the concentration of SARS-CoV-2 antibodies in the fatal group. (C) Correlations between ELISA and MSD V-PLEX SARS-CoV-2 assay responses. Responses to the S2 subunit of HCoV-OC43 are strongly correlated with the MSD concentration of SARS-CoV-2 antibodies in those who died from COVID-19 but not those who survived. Notably, there is a positive correlation between the S2 subunit response and the HCoV-OC43 and HCoV-HKU1 spike responses in the fatal COVID-19 outcome group. t tests were used to assess significance, and the reported P values were adjusted for multiple comparisons using the Holm-Bonferroni method, in A. Spearman’s rank correlations (ρ) are shown for each pair of antigens in B and C.