Figure 3.
Heterotypic RBD boost restores protection against 501Y.V2 in passively immunized k18-hACE2 mice
(A and B) Weight loss following challenge with either (A) “wild-type” (“WT”) or (B) 501Y.V2 virus for K18-hACE2 mice passively immunized with macaque plasma sampled post-S or post-vRBD. Control mice mock immunized with PBS and subsequently challenged (“PBS”) are shown in black, and uninfected littermates housed in the same cages (“uninfected”) are shown in gray.
(C) Pseudovirus-neutralizing antibody titers against the challenge spike (infective dose 50 [ID50]) in passively immunized mice on the day of challenge are associated with infection and disease severity summarized as weight loss 6 days following challenge. Titers below the limit of detection of the assay (20) are plotted as 10.
(D) Weight loss at day 6 for each group. Unchallenged littermates housed in the same cages (gray) are shown; PBS, mock immunized mice (black). Post-S, passive immunization with plasma following the second spike immunization (6-week plasma); post-vRBD, passive immunization with plasma from macaques boosted with variant (beta) RBD (31- or 32-week plasma). Groups displaying significant weight loss compared to uninfected mice are annotated above the points for that group.
(E) Viral loads in lung tissue on day 14 quantified as the ratio of the copies of either viral genomic envelope (E) or subgenomic transcripts (sgE) to the number of copies of housekeeping gene ABL1. Undetectable copies are plotted on the baseline (1 × 10−5).
(F) Pulmonary pathology scores in H&E-stained lung sections (89 slides in total, with a mean of 3.3 slides per mouse; range: 2–5). All statistical comparisons are summarized as ∗∗p < 0.01 and ∗∗∗p < 0.001; ns, not significant. Error bars depict SDs.