Structural analysis of full-length SARS-CoV-2 spike protein from an advanced vaccine candidate

Vaccine efforts to combat the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),which is responsible for the current coronavirus disease 2019(COVID-19)pandemic,are focused on SARS-CoV-2 spike glycoprotein,the primary target for neutralizing antibodies.We performed cryo-election microscopy and site-specific glycan analysis of one of the leading subunit vaccine candidates from Novavax,which is based on a full-length spike protein formulated in polysorbate 80 detergent.Our studies reveal a stable prefusion conformation of the spike immunogen with slight differences in the S1 subunit compared with published spike ectodomain structures.We also observed interactions between the spike trimers,allowing formation of higher-order spike complexes.This study confirms the structural integrity of the full-length spike protein immunogen and provides a basis for interpreting immune responses to this multivalent nanoparticle immunogen.