Figure 8. Neutralization of SARS‐CoV‐2 with symmetry‐matched VHH antibodies.

1. Left: Schematic representation of VHH antibodies produced in E. coli as monomers or homo‐trimeric fusions with the human collagen XVIII trimerization module. The VHH trimers match the threefold rotational symmetry of the SARS‐CoV‐2 Spike protein. The molecular weight of the indicated modules is shown. Right: As an example, monomeric and trimeric forms of Re7H02 (a Re6B06 class member, Fig 1A) were analyzed by size exclusion chromatography (SEC, Superdex 200 column) coupled with multi‐angle light scattering (MALS). The elution profiles (UV absorbance signal), as well as the calculated molecular weights (per slice), are plotted, and the average molecular weight is indicated.
2. Re6B06 monomer and trimer variants (20 nM) were analyzed by BLI for RBD‐binding, with 900 s association and 1,500 s dissociation steps. Note the avidity effect of Re6B06 trimerization.
3. Neutralization of SARS‐CoV‐2 by the indicated VHH antibodies. The neutralization experiment was performed as described in Fig 3A. Note the gain in neutralization efficacy when a VHH is trimerized. Re6B06, for example, is 30,000‐fold more potent when symmetry‐matched with the virus Spike.