Fig. 6: Nsp1-K164A/H165A vaccination protects against lung pathology post-challenge with Delta and Omicron isolates.

Syrian hamsters were vaccinated with a low (100 PFU) dose of Nsp1-K164A/H165A or WA1/2020 35 days prior to challenge with Delta or BA.1 Omicron isolates on day 0. Serial lung sections from non-infected non-vaccinated hamsters (mock) or 7 DPC-infected hamsters were stained by a H&E or double-immunostained for either b Iba1 (macrophage marker) and Prosurfactant protein C (ProSPC, AT2 marker) or c E-cadherin (ECAD, epithelial junctional marker) and RAGE (AT1 marker). Delta-infected unvaccinated lungs (n = 4) show extensive areas of tissue consolidation (a) that correspond with regions showing abundant Iba1-labeled macrophage accumulation and loss of ProSPC-labeled AT2 cells (b) as well as loss of alveolar wall RAGE-expressing AT1 epithelium surrounding affected ECAD-stained bronchioles and aberrant reepithelization (c). Similar though less extensive pathology was observed in two of four BA.1-challenged unvaccinated hamsters. Nsp1-K164A/H165A or WA1/2020 inoculation completely prevented or suppressed Delta or BA.1-induced lung pathology. In a, images are shown at one level of magnification (×0.7) while corresponding serial immunostained images in b and c are shown at three levels of magnification (×0.7, ×10, and ×40) with white boxes delimiting the regions of magnification. Nuclei were counterstained with Hoechst 33342 dye (blue). Scale bars: 5 mm (×0.7), 250 μm (×10), 100 μm (×40).