Antibody responses to endemic coronaviruses modulate COVID-19 convalescent plasma functionality

Abstract

COVID-19 convalescent plasma, particularly plasma with high-titer SARS-CoV-2 (CoV2) antibodies, is one of the leading treatments for individuals with early COVID-19 infection. The functionality of convalescent plasma varies greatly, but the association of antibody epitope specificities with plasma functionality remains uncharacterized. We assessed antibody functionality and reactivities to peptides across the CoV2 and the four endemic human coronavirus (HCoV) genomes in 126 COVID-19 convalescent plasma donations. We found strong correlation between plasma functionality and polyclonal antibody targeting of CoV2 spike protein peptides. Antibody reactivity to many HCoV spike peptides also displayed strong correlation with plasma functionality, including pan-coronavirus cross-reactive epitopes located in a conserved region of the fusion peptide. After accounting for antibody cross-reactivity, we identified an association between greater alphacoronavirus NL63 antibody responses and development of highly neutralizing antibodies to SARS-CoV-2. We also found that plasma preferentially reactive to the CoV2 spike receptor binding domain (RBD), versus the betacoronavirus HKU1 RBD, had higher neutralizing titer. Finally, we developed a two-peptide serosignature that identifies plasma donations with high anti-spike titer, but that suffer from low neutralizing activity. These results suggest that analysis of coronavirus antibody fine specificities may be useful for selecting therapeutic plasma with desired functionalities.

Relative Ratios of Human Seasonal Coronavirus Antibodies Predict the Efficiency of Cross-Neutralization of SARS-CoV-2 Spike Binding to ACE2

“…An even more interesting observation is how NL63 correlates with cross-reactive N IgGs (Fig. 6D), a similar observation was also made by another group (30). While N antibodies are unlikely to be neutralizing, their Fc effector function, their role in CD8+ T cell responses and /or the cytokines and immune factors involved in their production may all have an indirect influence on other antiviral pathways in a live infected host.…”

SARS-CoV-2 mRNA vaccines induce broad CD4+ T cell responses that recognize SARS-CoV-2 variants and HCoV-NL63

“…The percent sequence identity of the CCC spike proteins to SARS-CoV-2 spike protein has been estimated to be around 30% with the beta coronaviruses (HCoV-OC43 and HCoV-HKU1) having slightly higher identity than the alpha coronaviruses (HCoV-NL63 and HCoV-229E)(4). However, a recent study that analyzed antibodies to all 4 CCCs in plasma from convalescent COVID-19 patients revealed an association between HCoV-NL63 antibody responses and the development of highly neutralizing antibodies to SARS-CoV-2 (24) suggesting that HCoV-NL63 may have more epitopes in common with SARS-CoV-2 than the other CCCs.…”

SARS-CoV-2 Antigens Expressed in Plants Detect Antibody Responses in COVID-19 Patients

“…However, in SARS-CoV-2 infection, antibodies may not follow this typical pattern of seroconversion (Long et al, 2020;Seow et al, 2020) and seroconversion to a single Ig subclass has been described (Seow et al, 2020). SARS-CoV-2-specific antibodies are rapidly and readily induced after infection, but the kinetics may be influenced by multiple factors, such as cross-reactive serum antibodies as well as memory B cells from hCoVs (Hartley et al, 2020;Morgenlander et al, 2021). This appears similar to other hCoVs, including SARS-CoV and MERS-CoV (Huang et al, 2020).…”