National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)
R01 AI146779
米国
Other government
Massachusetts Consortium on Pathogenesis Readiness (MassCPR)
米国
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
T32 GM007753
米国
引用
ジャーナル: bioRxiv / 年: 2021 タイトル: Rationally designed immunogens enable immune focusing to the SARS-CoV-2 receptor binding motif. 著者: Blake M Hauser / Maya Sangesland / Kerri J St Denis / Ian W Windsor / Jared Feldman / Evan C Lam / Ty Kannegieter / Alejandro B Balazs / Daniel Lingwood / Aaron G Schmidt 要旨: Eliciting antibodies to surface-exposed viral glycoproteins can lead to protective responses that ultimately control and prevent future infections. Targeting functionally conserved epitopes may help ...Eliciting antibodies to surface-exposed viral glycoproteins can lead to protective responses that ultimately control and prevent future infections. Targeting functionally conserved epitopes may help reduce the likelihood of viral escape and aid in preventing the spread of related viruses with pandemic potential. One such functionally conserved viral epitope is the site to which a receptor must bind to facilitate viral entry. Here, we leveraged rational immunogen design strategies to focus humoral responses to the receptor binding motif (RBM) on the SARS-CoV-2 spike. Using glycan engineering and epitope scaffolding, we find an improved targeting of the serum response to the RBM in context of SARS-CoV-2 spike imprinting. Furthermore, we observed a robust SARS-CoV-2-neutralizing serum response with increased potency against related sarbecoviruses, SARS-CoV, WIV1-CoV, RaTG13-CoV, and SHC014-CoV. Thus, RBM focusing is a promising strategy to elicit breadth across emerging sarbecoviruses and represents an adaptable design approach for targeting conserved epitopes on other viral glycoproteins. ONE SENTENCE SUMMARY: SARS-CoV-2 immune focusing with engineered immunogens.