Key result
The novel antibody fragment VH ab6 broadly neutralizes major SARS-CoV-2 variants of concern by binding to a highly conserved epitope on the receptor-binding domain.
Why the study?
Mutations in the spike glycoproteins of SARS-CoV-2 variants of concern enhance aspects of spike protein fitness, warranting investigation into broad neutralization vulnerabilities.
The discovery of the VH ab6 antibody fragment reveals a conserved vulnerability in the SARS-CoV-2 spike protein that allows for broad neutralization across major variants.
May enable pan-variant antibody development; leaves open clinical translation and efficacy trials.
Mutations in the spike glycoproteins of SARS-CoV-2 variants of concern have independently been shown to enhance aspects of spike protein fitness. Here, we report the discovery of a novel antibody fragment (V H ab6) that neutralizes all major variants, with a unique mode of binding revealed by cryo-EM studies. Further, we provide a comparative analysis of the mutational effects within variant spikes and identify the structural role of mutations within the NTD and RBD in evading antibody neutralization. Our analysis shows that the highly mutated Gamma N-terminal domain exhibits considerable structural rearrangements, partially explaining its decreased neutralization by convalescent sera. Our results provide mechanistic insights into the structural, functional, and antigenic consequences of SARS-CoV-2 spike mutations and highlight a spike protein vulnerability that may be exploited to achieve broad protection against circulating variants.
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Mannar et al. (2021) studied SARS-CoV-2. VH ab6 was evaluated on Neutralization of SARS-CoV-2 variants. The novel antibody fragment VH ab6 broadly neutralizes major SARS-CoV-2 variants of concern by binding to a highly conserved epitope on the receptor-binding domain.
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