Cells were incubated with sera (diluted 1:50 in PBS) for 30 min, washed with FACS buffer (PBS, 5% BSA, 0

Cells were incubated with sera (diluted 1:50 in PBS) for 30 min, washed with FACS buffer (PBS, 5% BSA, 0.05% sodium azide), and stained with BV421 anti-IgG (clone HP6017, Biolegend), Ulipristal acetate APC anti-IgM (clone MHM-88, Biolegend), and PE anti-IgA (clone IS11-8E10, Miltenyi Biotech) for 30 min (all antibodies diluted 1:200 in FACS buffer). was significantly more pronounced following B.1.1.7 than parental strain contamination. Conclusions: The results indicate that heterotypic immunity induced by SARS-CoV-2 variants is asymmetric. Funding: This work was supported by the Francis Crick Institute and the Max Planck Institute for Dynamics of Complex Technical Systems, Magdeburg. Research organism: Human, Computer virus Introduction Mutations in severe acute respiratory syndrome?coronavirus?2 (SARS-CoV-2) variants that arose in the United Kingdom (UK) (B.1.1.7; Rabbit polyclonal to AKAP5 Alpha) or in South Africa (B.1.351; Beta) reduce recognition by antibodies elicited by natural infection with the parental reference (Wuhan) strain Ulipristal acetate and the subsequent D614G variant (Cele et al., 2021; Diamond et al., 2021; Edara et al., 2021; Emary et al., 2021; Liu et al., 2021b; Planas et al., 2021; Skelly et al., 2021; Wang et al., 2021; Wibmer et al., 2021; Zhou et al., 2021). Such reduction in cross-reactivity also impinges the effectiveness of current vaccines based on the Wuhan strain (Diamond et al., 2021; Edara et al., 2021; Emary et al., 2021; Liu et al., 2021b; Skelly et al., 2021; Wang et al., 2021; Zhou et al., 2021), prompting concern of option vaccines based on the new variants. However, the immunogenicity of the latter or, indeed, the degree of heterotypic immunity the new variants may afford remains to be established. Results and Discussion The B.1.1.7 variant is thought to have first emerged in the UK in September 2020 Ulipristal acetate and has since been detected in over 50 countries (Kirby, 2021). To examine the antibody response to B.1.1.7, we collected sera from 29 patients, admitted to University College?London Hospitals (UCLH) for unrelated reasons (Supplementary file 1), who had confirmed B.1.1.7 infection. The majority (23/29) of these patients displayed relatively moderate COVID-19 symptoms and a smaller number (6/29) remained COVID-19-asymptomatic. As antibody titres may depend on the severity of SARS-CoV-2 contamination, as well as on time since contamination (Gaebler et al., 2021; Long et al., 2020), we compared B.1.1.7 sera with sera collected during the first wave of D614G variant spread in London from hospitalised COVID-19 patients (Ng et al., 2020) (n=20) and moderate/asymptomatic SARS-CoV-2-infected health care workers (Houlihan et al., 2020) (n=17) who were additionally sampled 2 months later. IgG, IgM, and IgA antibodies to the spikes of the Wuhan strain or of variants D614G, B.1.1.7, or B.1.351, expressed on HEK293T cells, were detected by a flow cytometry-based method (Physique 1; Physique 1figure supplement 1; Ng et al., 2020). Titres of antibodies that bound the parental D614G spike largely correlated with those that bound the B.1.1.7 or B.1.351 spikes (Figure 1aCc), consistent with the high degree of similarity. Comparable correlations were observed for all those three Ig classes also between the Wuhan strain and the three variant spikes and between the B.1.1.7 and B.1.351 spikes (Figure 1figure supplements 2C5). Open in a separate window Physique 1. Recognition of distinct severe acute respiratory syndrome?coronavirus?2 (SARS-CoV-2) spike glycoproteins by antibodies in D614G and B.1.1.7 sera.(a-c) Correlation of IgG (a), IgM (b), and IgA (c) antibody levels to D614G and B.1.1.7 or B.1.351 spikes in the indicated groups of donors infected either with the D614G or B.1.1.7 strains. Each symbol represents an individual sample and levels are expressed as a percentage of the positive control. Black lines denote complete correlation and grey lines a 25% change in either direction. (d-f) Comparison of IgG (d), IgM (e), and IgA (f) antibody levels to the indicated spikes in groups of donors acutely infected either with the D614G or B.1.1.7 strains. Connected Ulipristal acetate symbols represent individual donors. Numbers above the plots denote the average binding to each spike, expressed as a percentage.