Fig. 8: Seroconverted sentinel hamsters (i.e. passively vaccinated through transmission of Nsp1-K164A/H165A) are protected from BA.2.12.1 challenge.

a Seroconverted sentinel hamsters (4.5 months after exposure to WA1-2020 and Nsp1- K164A/H165A) were challenged with 10⁴ PFU of BA.2.12.1. A group of 8 age-matched naïve hamsters were also included in the challenge study as controls. Weight change was recorded for 7 days post-challenge. b–d Infectious virus titers from nasal swabs (*p = 0.0393, *p = 0.0416, **p = 0.0059, ***p = 0.0008) (b), BALF (c), and lung homogenates (d) were measured by focus-forming assays. e Viral sgRNA levels in the lungs were quantified by RT-pPCR 4 DPC and 7 DPC (**p = 0.0043, ***p = 0.0004). Dot plots represent samples collected from individual animals in a single experiment. Percentage of consolidation (*p = 0.0490, *p = 0.0326, *p = 0.0269) (f) and pathology scores in lungs (g) of sentinel hamsters (n = 6 for Nsp1-K164A/H165A, n = 7 for WA1/2020, and n = 8 for naïve controls) at 4 and 7 DPC with 10⁴ PFU of BA.2.12.1. Individual lung pathologies at 4 DPC (h) and 7 DPC (i) are presented in heat maps. Dot plots in this graph represent samples collected from individual animals in a single experiment. Statistical differences were calculated using ordinary two-way analysis of variance (ANOVA) in GraphPad Prism 9.4.0 with Tukey’s multiple comparisons tests. For statistical significance, ****p < 0.0001. DPC days post-challenge.