+検索条件
-Structure paper
タイトル | Rationally designed immunogens enable immune focusing following SARS-CoV-2 spike imprinting. |
---|---|
ジャーナル・号・ページ | Cell Rep, Vol. 38, Issue 12, Page 110561, Year 2022 |
掲載日 | 2022年3月22日 |
著者 | Blake M Hauser / Maya Sangesland / Kerri J St Denis / Evan C Lam / James Brett Case / Ian W Windsor / Jared Feldman / Timothy M Caradonna / Ty Kannegieter / Michael S Diamond / Alejandro B Balazs / Daniel Lingwood / Aaron G Schmidt / |
PubMed 要旨 | Eliciting antibodies to surface-exposed viral glycoproteins can generate protective responses that control and prevent future infections. Targeting conserved sites may reduce the likelihood of viral ...Eliciting antibodies to surface-exposed viral glycoproteins can generate protective responses that control and prevent future infections. Targeting conserved sites may reduce the likelihood of viral escape and limit the spread of related viruses with pandemic potential. Here we leverage rational immunogen design to focus humoral responses on conserved epitopes. Using glycan engineering and epitope scaffolding in boosting immunogens, we focus murine serum antibody responses to conserved receptor binding motif (RBM) and receptor binding domain (RBD) epitopes following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike imprinting. Although all engineered immunogens elicit a robust SARS-CoV-2-neutralizing serum response, RBM-focusing immunogens exhibit increased potency against related sarbecoviruses, SARS-CoV, WIV1-CoV, RaTG13-CoV, and SHC014-CoV; structural characterization of representative antibodies defines a conserved epitope. RBM-focused sera confer protection against SARS-CoV-2 challenge. Thus, RBM focusing is a promising strategy to elicit breadth across emerging sarbecoviruses without compromising SARS-CoV-2 protection. These engineering strategies are adaptable to other viral glycoproteins for targeting conserved epitopes. |
リンク | Cell Rep / PubMed:35303475 / PubMed Central |
手法 | EM (単粒子) / X線回折 |
解像度 | 3.5 - 9.2 Å |
構造データ | EMDB-24894: Ab16 Fab in complex with SARS-CoV-2 Spike (6P) EMDB-24895: Ab20 in complex with SARS-CoV-2 spike (6P) PDB-7te1: |
由来 |
|
キーワード | IMMUNE SYSTEM/Viral Protein / antibody-antigen complex / SARS-CoV-2 / receptor binding domain / IMMUNE SYSTEM / IMMUNE SYSTEM-Viral Protein complex |