Thread by @veeslerlab

The #SARSCoV2 CAL20.C (B.1.427/B.1.429) variant is skyrocketing in California. We describe how it evades the host immune response with @DavideCorti6 @LucaPiccoli9

Led by @Dr_MattMcCallum, Jessica Bassi, Anna De Marco, Alex Chen & @coronalexington

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biorxiv.org/content/10.110…

The #SARSCoV2 CAL20.C (B.1.427/B.1.429) variant comprises 3 spike mutations: S13I, W152C & L452R reducing plasma neutralizing activity by ~3x and ~5x for vaccine- and infection-elicited antibodies (Abs), compared to the 'ancestral' virus.

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The neutralization potency of 1/3 of RBD Abs is reduced or abrogated by the L452R spike mutation present in #SARSCoV2 CAL20.C (B.1.427/B.1.429), including clinical-stage antibodies such as Eli Lilly LY-CoV555 (bamlanivimab) & Celltrion CT-P59 (regdanvimab)

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These data concur with deep-mutational scanning data from @tylernstarr @AllieGreaney @AdamDingens & @jbloom_lab

biorxiv.org/content/10.110…

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Moreover, the neutralizing activity of all NTD antibodies tested was completely abrogated by the spike S13I and W152C mutations indicating this variant of concern found yet another solution for evading these types of antibodies.

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Specifically, the S13I and W152C mutations lead to loss of NTD mAb binding, due to deletion of the spike 2 N-term residues (S13I-mediated shift of the signal peptide cleavage site) and rearrangement of the NTD through formation of a new C136-W152C disulfide bond.

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These data clearly demonstrate the importance of #SARSCoV2 spike signal peptide mutants in a clinical setting and warrant close monitoring of such variants and their involvement in immune evasion.

Thanks Mary-Jane Navarro @aletortorici @johnbowenbio and all collaborators!

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