Atypical Antibody Dynamics During Human Coronavirus HKU1 Infections

Abstract

Human coronavirus HKU1 (HCoV-HKU1) is one of the four endemic coronaviruses. It has been suggested that there is a difference in incidence, with PCR-confirmed HCoV-NL63 and HCoV-OC43 infections occurring more commonly, whereas HCoV-HKU1 is the least seen. Lower incidence of HCoV-HKU1 infection has also been observed in serological studies. The current study aimed to investigate antibody dynamics during PCR-confirmed HCoV-HKU1 infections using serum collected during infection and 1 month later. We expressed a new HCoV-HKU1 antigen consisting of both the linker and carboxy-terminal domain of the viral nucleocapsid protein and implemented it in ELISA. We also applied a spike-based Luminex assay on serum samples from PCR-confirmed infections by the four endemic HCoVs. At least half of HCoV-HKU1-infected subjects consistently showed no antibody rise via either assay, and some subjects even exhibited substantial antibody decline. Investigation of self-reported symptoms revealed that HCoV-HKU1-infected subjects rated their illness milder than subjects infected by other HCoVs. In conclusion, HCoV-HKU1 infections reported in this study displayed atypical antibody dynamics and milder symptoms when compared to the other endemic HCoVs.

Keywords: HCoV-229E; HCoV-HKU1; HCoV-NL63; HCoV-OC43; IgG response; endemic seasonal coronavirus; nucleocapsid protein; spike protein.

FIGURE 1

(A) Location of Nt-, Ct-, and linker (L)-domain of HCoV-HKU1 N as determined by pairwise alignment with HCoV-OC43, as well as the comparison of size between HKU1-NLCt and the HKU1-NCt antigen. (B) Multiple alignment of the nucleocapsid L domain of HCoV-NL63, HCoV-229E, HCoV-OC43, and HCoV-HKU1. The symbols below the aligned amino acid sequence represent the consensus symbol of amino acid residue at each position: asterisks (*) denotes fully conserved residue, colons (:) denotes amino acid residues with strongly similar property, periods (.) denotes amino acid residues with weakly similar property, and the absence of symbol denotes completely different property.

FIGURE 2

(A) V1-V2 Fold change in antibody values of 54 subjects with PCR-confirmed endemic HCoV infection, as assayed with ELISA with matched N antigen. For HCoV-HKU1-infections, both HKU1-NLCt (half-filled red circles) and HKU1-NCt (full red circles) were used for the N assay. Dotted line represents cutoff of significant antibody rise (fold change of 1.40 or higher). The NCt ELISA fold change values for all four endemic coronaviruses have been published previously Edridge et al. (2020). (B) V1-V2 Fold change in antibody values using matched S antigens for each HCoV infection in the S-Luminex assay. Dotted line represents the cutoff of significant S-antibody rise (fold change of 2.01 or higher).