Evaluating the immunogenicity of clade 2 and clade 3 sarbecovirus spike protein nanoparticle vaccines in Syrian...

The emergence of SARS-CoV-2 in human circulation in 2019 led to a push for universal coronavirus vaccine development. While many vaccine candidates against SARS-like viruses focus on close relatives of SARS-CoV-1 and SARS-CoV-2, more distant viruses in Sarbecovirus clades 2 and 3 have received less attention in vaccine studies. Here, we evaluate in hamsters the immunogenicity of nanoparticle vaccines displaying the spike proteins from clade 2 viruses Yunnan2011, YN2013, and HKU3-8 and from the clade 3 virus BtKY72. We find that our nanoparticle vaccines elicit pan-sarbecovirus reactivity in vaccinated hamster sera, although this binding is clade-biased. Hamster antisera from BtKY72 VLP-S vaccination potently neutralizes authentic SHC014 bat coronavirus, but both clade 2 and clade 3 antisera fail to neutralize authentic WIV1 bat coronavirus or the SARS-CoV-2 XBB variant. All vaccine groups provide limited but significant protection against a challenge with XBB virus.