Figure 2.
Heterotypic RBD boost drives a potent cross-neutralizing antibody response
(A) Neutralizing antibody responses over time to Wu-Hu-1 (blue) and beta (red) pseudotyped viruses (PSVs) are shown for three immunized macaques: H05; H06; and H07. Syringes indicate the timing of immunizations (blue: Wu-Hu-1 spike at 0 and 4 weeks; red: beta RBD at 30 weeks). Titers from 27 to 30 weeks (shown with dashed lines) have been extrapolated for clarity. Error bars depict the geometric SD from at least 3 technical repeats.
(B) Although PSV neutralization (reduction in infectivity, as a %) of beta was significantly reduced at 6 weeks, corresponding to peak responses 2 weeks following the second spike dose (post-S), neutralization was restored following subsequent heterotypic RBD boost (post-vRBD) such that beta (red) and Wu-Hu-1 (blue) were potently neutralized at similar titers in all three animals. Error bars depict the SD from at least 3 technical repeats.
(C) Heterotypic RBD boost also restored the reduced neutralizing antibody titers against VOCs alpha (green), gamma (yellow), and delta (orange) as well as improved the neutralization of the more distantly related SARS-CoV-1 (open circles).
(D) Depiction of the RBD immunogen (PDB: 6MOJ),22 used as a heterotypic boost in this study, that incorporates the three RBD mutations (located in red) defining lineage 20H/501Y.V2 (beta). The cellular receptor, ACE2, is shown in green.