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[Preprint]. 2024 Oct 23:2024.10.23.619886.
doi: 10.1101/2024.10.23.619886.

Recent Endemic Coronavirus Infection Associates With Higher SARS-CoV-2 Cross-Reactive Fc Receptor Binding Antibodies

David J Bean  1 , Yan Mei Liang  2 , Manish Sagar  1   2
Affiliations

Recent Endemic Coronavirus Infection Associates With Higher SARS-CoV-2 Cross-Reactive Fc Receptor Binding Antibodies

David J Bean et al. bioRxiv. .

Abstract

Recent documented infection with an endemic coronavirus (eCoV) associates with less severe coronavirus disease 2019 (COVID-19), yet the immune mechanism behind this protection has not been fully explored. We measured both antibody and T cell responses against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in SARS-CoV-2 naïve individuals classified into two groups, either with or without presumed recent eCoV infections. There was no difference in neutralizing antibodies and T cell responses against SARS-CoV-2 antigens between the two groups. SARS-CoV-2 naïve individuals with recent presumed eCoV infection, however, had higher levels of Fc receptor (FcR) binding antibodies against eCoV spikes (S) and SARS-CoV-2 S2. There was also a significant correlation between eCoV and SARS-CoV-2 FcR binding antibodies. Recent eCoV infection boosts cross-reactive antibodies that can mediate Fc effector functions, and this may play a role in the observed heterotypic immune protection against severe COVID-19.

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Conflict of interest statement

The authors have declared that no conflict of interest exists.

Figures

Figure 1.
Figure 1.. Classification of presumed SARS-CoV-2 infections based on antibody levels.
(A) IgG antibody levels against SARS-CoV-2 RBD and nucleocapsid protein were measured in individuals with a previous SARS-CoV-2 infection (black), previous COVID-19 vaccination with no documented history of SARS-CoV-2 infections (pink), no known SARS-CoV-2 infection or COVID-19 vaccination (green), or pre-pandemic samples collected before March 2020 (purple). The dotted lines specify cutoffs that were established to classify individuals with presumed undiagnosed SARS-CoV-2 infection. (B) The accuracy and other test characteristics of the classification based on the established cutoffs for classifying individuals into the specified groups. The values in parentheses display the 95% CI.
Figure 2.
Figure 2.. Humoral immune responses to SARS-CoV-2 spike antigens.
Plasma antibody responses in those with documented SARS-CoV-2 spike exposure (previous SARS-CoV-2 infection (black circle) or prior COVID-19 vaccination (black square)), presumed or documented recent eCoV infection (gray circle), or without a presumed recent eCoV infection (white circle). (A and B) IgG antibody levels against SARS-CoV-2 RBD (A) or SARS-CoV-2 spike S2 subunit (B). (C) Neutralization responses against a VSV-ΔG pseudovirus expressing the SARS-CoV-2-Wuhan spike protein. (D-G) Titer of SARS-CoV-2 RBD (D) or SARS-CoV-2 S2 (F) specific antibodies binding to the Fc receptor, FcγRIIIa, or the ratio of those FcR binding antibodies to the SARS-CoV-2 RBD (E) or SARS-CoV-2 S2 (G) IgG levels in panel (A and B). The dark horizontal lines in each scatter dot plot denote the median and interquartile range. Statistical analyses were performed using either Kruskal-Wallis test with Dunn multiple comparison test or Mann-Whitney U test. P-values less than 0.1 are displayed. *, **, ***, and **** represent p-values <0.05, <0.01, <0.001, and <0.0001, respectively.
Figure 3.
Figure 3.. Higher alpha eCoV nucleocapsid antibody responses predicts positive responses in the SARS-CoV-2 S2 specific antibody FcR binding assay.
(A) Individuals were separated into two groups based on positive (responders) or absent (non-responders) FcγRIIIa SARS-CoV-2 S2 specific antibody binding. This responder and non-responder classification was used in a multivariate logistic regression model. This data is the same as Fig. 2F. (B) The odds ratio of variables used in the multivariate logistic regression model to predict positive SARS-CoV-2 S2 antibody FcR binding responses. The error bars represent the 95% CI.
Figure 4.
Figure 4.. ECoV specific antibody FcR binding responses correlate with SARS-CoV-2 S2 antibody responses.
Plasma antibody responses were measured in individuals with either a previous SARS-CoV-2 spike exposure (previous SARS-CoV-2 infection (black circle) and previous COVID-19 vaccination (black square)), presumed or documented recent eCoV infection (gray circle), or without a presumed recent eCoV infection (white circle). (A and B) IgG antibody responses against HCoV-229E (A) or HCoV-OC43 (B) spikes. (C and D) Level of HCoV-229E (C) or HCoV-OC43 (D) spike-specific antibodies binding to the Fc receptor, FcγRIIIa. (E and F) Ratio of Fc receptor antibody binding (C and D) to antigen specific IgG (A and B) in HCoV-229E (E) or HCoV-OC43 (F) spike-specific antibody responses. (G and H) Correlations between HCoV-229E (E) or HCoV-OC43 (F) spike-specific antibody FcR binding to SARS-CoV-2 S2 specific antibody FcR binding responses. Black dots and lines represent individuals with presumed or documented recent eCoV infection, while gray represents those without a presumed recent eCoV infection. The lines show a simple linear regression with the 95% CI. The dark horizontal lines in each scatter dot plot denote the median and interquartile range. Statistical analyses were performed using either Kruskal-Wallis test with Dunn multiple comparison test or Mann-Whitney U test. P-values less than 0.1 are displayed. * represents p-values <0.05.
Figure 5.
Figure 5.. T cell responses against SARS-CoV-2 antigens are similar between individuals with or without presumed recent eCoV infections.
T cell responses were measured in individuals with either a previous SARS-CoV-2 spike exposure (previous SARS-CoV-2 infection (black circle) and previous COVID-19 vaccination (black square)), presumed or documented recent eCoV infection (gray circle), or without a presumed recent eCoV infection (white circle). Cells were stimulated with SARS-CoV-2 peptide pools and percent of activated (CD134+ CD137+) CD4+ T cells and (CD69+ CD137+) CD8+ T cells were measured. (A-B) CD4+ (A) and CD8+ (B) T cell activation was measured after stimulation with SARS-CoV-2 spike peptides. (C-D) CD4+ (C) and CD8+ (D) T cell activation was measured after stimulation with SARS-CoV-2 nucleocapsid peptides. (E-F) CD4+ (E) and CD8+ (F) T cell activation was measured after stimulation with SARS-CoV-2 nsp12/nsp13 peptides. Data were background subtracted against the negative control (DMSO only). The dark horizontal lines in each scatter dot plot denote the median and interquartile range. Note, the y axis varies among the different panels. Statistical analyses were performed using either Kruskal-Wallis test with Dunn multiple comparison test or Mann-Whitney U test. P-values less than 0.1 are displayed. *, **, ***, and **** represent p-values <0.05, <0.01, <0.001, and <0.0001, respectively.
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