pmed.1003656.g005.tif (3.14 MB)

SARS-CoV-2 antibody responses show evasion by emerging Spike variants.

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posted on 2021-07-06, 17:42 authored by Fiona Tea, Alberto Ospina Stella, Anupriya Aggarwal, David Ross Darley, Deepti Pilli, Daniele Vitale, Vera Merheb, Fiona X. Z. Lee, Philip Cunningham, Gregory J. Walker, Christina Fichter, David A. Brown, William D. Rawlinson, Sonia R. Isaacs, Vennila Mathivanan, Markus Hoffmann, Stefan Pöhlman, Ohan Mazigi, Daniel Christ, Dominic E. Dwyer, Rebecca J. Rockett, Vitali Sintchenko, Veronica C. Hoad, David O. Irving, Gregory J. Dore, Iain B. Gosbell, Anthony D. Kelleher, Gail V. Matthews, Fabienne Brilot, Stuart G. Turville

(A) Most patients had broad recognition of Spike variants (blue), whereas a smaller group had restricted Spike variant recognition and did not have a strong immunoreactivity to D614G Spike (red). Patients with reduced binding to D614G Spike had lower virus–cell fusion (ADAPT P < 0.01, LIFE P < 0.05) and neutralization scores (ADAPT P < 0.0001, LIFE P < 0.05) (B) and presented with less broad polyantigenic SARS-CoV-2 recognition (C). (D) D614G Spike-binding sera had greater inhibition of D614G Spike-pseudotyped virus–cell fusion (ns). (E) In Australia, D614G Spike was the predominant variant during the first wave and acquired additional mutations during the second wave (S477N, V1068F). VOCs, with high mutations within Spike, appeared in late December 2021. Pango lineages and Clades are shown in brackets. Graph adapted from Nextstrain [54]. (F) All patients had decreased immunoreactivity to S477N/D614G and S477N/D614G/V1068F Spike, while V1068F did not have an additive effect (ns, not significant). (G) Patients had reduced virus–cell fusion inhibition (first wave P < 0.0001, second wave P < 0.05) and neutralization (first wave P < 0.01, second wave ns) (H) to the S477N/D614G Spike variant compared to D614G. (I) Patients had reduced binding to VOC B.1.1.7 (UK) and B.1.351 (SA) Spike, with greater reduction toward B.1.351 (first wave P < 0.0001, second wave P < 0.0001). Virus–cell fusion inhibition (J) and neutralization (K) was also reduced against the VOC B.1.1.7 (UK, (J) first wave P < 0.0001, second wave P < 0.0001; (K) first wave P < 0.01, second wave ns) and B.1.351 (SA), but more so against the VOC B.1.351 (SA, (J) first wave P < 0.0001, second wave P < 0.05; (K) first wave P < 0.00001, second wave P < 0.0001). (L) Reduced neutralization was also observed against the authentic VOC B.1.1.28.1 (Brazil) (first wave P < 0.00001, second wave P < 0.01) and B.1.1.28.2 (Brazil) (first wave P < 0.00001, second wave P < 0.01). The level of decreased binding (F, I), virus–cell fusion inhibition (G, J), and neutralization (H, K) was irrespective of the virus that infected patients during the second wave. PCR, polymerase chain reaction; SARS-CoV-2, Severe Acute Respiratory Syndrome Coronavirus 2; VOC, variant of concern.