Distinct Antibody Responses to Endemic Coronaviruses Pre- and Post-SARS-CoV-2 Infection in Kenyan Infants and Mothers

Abstract

Pre-existing antibodies that bind endemic human coronaviruses (eHCoVs) can cross-react with SARS-CoV-2, which is the betacoronavirus that causes COVID-19, but whether these responses influence SARS-CoV-2 infection is still under investigation and is particularly understudied in infants. In this study, we measured eHCoV and SARS-CoV-1 IgG antibody titers before and after SARS-CoV-2 seroconversion in a cohort of Kenyan women and their infants. Pre-existing eHCoV antibody binding titers were not consistently associated with SARS-CoV-2 seroconversion in infants or mothers; however, we observed a very modest association between pre-existing HCoV-229E antibody levels and a lack of SARS-CoV-2 seroconversion in the infants. After seroconversion to SARS-CoV-2, antibody binding titers to the endemic betacoronaviruses HCoV-OC43 and HCoV-HKU1, and the highly pathogenic betacoronavirus SARS-CoV-1, but not the endemic alphacoronaviruses HCoV-229E and HCoV-NL63, increased in the mothers. However, eHCoV antibody levels did not increase following SARS-CoV-2 seroconversion in the infants, suggesting the increase seen in the mothers was not simply due to cross-reactivity to naively generated SARS-CoV-2 antibodies. In contrast, the levels of antibodies that could bind SARS-CoV-1 increased after SARS-CoV-2 seroconversion in both the mothers and infants, both of whom were unlikely to have had a prior SARS-CoV-1 infection, supporting prior findings that SARS-CoV-2 responses cross-react with SARS-CoV-1. In summary, we found evidence of increased eHCoV antibody levels following SARS-CoV-2 seroconversion in the mothers but not the infants, suggesting eHCoV responses can be boosted by SARS-CoV-2 infection when a prior memory response has been established, and that pre-existing cross-reactive antibodies are not strongly associated with SARS-CoV-2 infection risk in mothers or infants.

Risk Factors of Severe COVID-19: A Review of Host, Viral and Environmental Factors

“…The molecular targets are mainly the S [ 704 , 705 , 711 , 712 , 713 ] and N proteins [ 694 , 704 , 705 , 713 , 714 ], but cross-recognition of conserved non-structural proteins [ 704 ] has also been reported. These antibodies recognize SARS and MERS coronaviruses [ 712 ] along with seasonal HCoV antigens [ 694 , 711 , 712 , 714 , 715 , 716 ], indicating broad cross-reactivity. Due to closer relatedness, the probability to cross-react to SARS-CoV-2 might be higher for immune responses that had been elicited against HCoVs belonging to the betacoronaviruses compared to those that targeted earlier alphacoronavirus infections.…”

“…However, while some studies demonstrated this effect for antibody levels against all seasonal HCoVs [ 717 , 718 , 719 ], in others the effect was limited to titers against betacoronaviruses [ 720 , 721 , 722 , 723 ] (especially HCoV-OC43 [ 707 , 724 , 725 , 726 , 727 ]), or surprisingly, to alphacoronaviruses only [ 728 , 729 ]. Independent of the level of antibodies, SARS-CoV-2-specific IgG and IgM were shown to robustly recognize betacoronavirus antigens [ 712 , 715 , 730 ].…”

Elevated binding and functional antibody responses to SARS-CoV-2 in infants versus mothers

“…Mother-infant pairs enrolled in an existing prospective cohort of mother-to-child virome transmission in Nairobi, Kenya (the Linda Kizazi study) were consented to SARS-CoV-2 testing as described previously (Begnel et al, 2023; Stoddard et al, 2022). Mothers and infants attended clinic visits approximately every 3 months, at which time clinical data and samples including blood were collected.…”

“…Multiplexed chemiluminescent antibody binding assay SARS-CoV-2 Spike, RBD, NTD and nucleocapsid IgG antibody levels were detected using a commercially available multiplexed chemiluminescent binding assay (Mesoscale Diagnostics, MSD), as previously described (Stoddard et al, 2022). Briefly, plasma samples were heat-inactivated for 60 minutes at 56°C and diluted 1:5000 according to the manufacturer's instructions.…”

“…As previously mentioned, only samples that were positive by SARS-CoV-2 Nucleocapsid ELISA were included in the study. In addition, a within-assay positivity threshold was set for each SARS-CoV-2 antigen in the MSD assay by measuring the mean AU/mL plus three standard deviations above the mean among a population of 18 pre-pandemic samples collected as part of the Linda Kizazi study (Stoddard et al, 2022). Measurements in the experimental (SARS-CoV-2 positive) population that fell below this threshold were set to the midpoint between zero and the threshold.…”