National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)
R01 AI146779
米国
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)
F30 AI160908
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: Cell Rep / 年: 2022 タイトル: Rationally designed immunogens enable immune focusing following SARS-CoV-2 spike imprinting. 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 ...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 / 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.
根拠: surface plasmon resonance, Biolayer interferometry was performed to determine the binding kinetics of the Ab17 Fab to the SARS-CoV-2 receptor binding domain.
タイプ
名称
対称操作
数
identity operation
1_555
x,y,z
1
単位格子
Length a, b, c (Å)
207.931, 207.931, 86.662
Angle α, β, γ (deg.)
90.000, 90.000, 90.000
Int Tables number
92
Space group name H-M
P41212
Space group name Hall
P4abw2nw
-
要素
#1: 抗体
Ab17heavychain
分子量: 23975.820 Da / 分子数: 2 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 細胞株: HEK 293-F / 細胞株 (発現宿主): HEK 293-F / 発現宿主: Homo sapiens (ヒト)
#2: 抗体
Ab17lightchain
分子量: 23363.680 Da / 分子数: 2 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 細胞株 (発現宿主): HEK 293-F / 発現宿主: Homo sapiens (ヒト)