Author: Brian G. Pierce; Zhen-Yong Keck; Ruixue Wang; Patrick Lau; Kyle Garagusi; Khadija Elkholy; Eric A. Toth; Richard A. Urbanowicz; Johnathan D. Guest; Pragati Agnihotri; Melissa C. Kerzic; Alexander Marin; Alexander K. Andrianov; Jonathan K. Ball; Roy A. Mariuzza; Thomas R. Fuerst; Steven K.H. Foung
Title: Structure-based design of hepatitis C virus E2 glycoprotein improves serum binding and cross-neutralization Document date: 2020_4_17
ID: b6to1v4u_5
Snippet: There have been a number of successful structure-based vaccine designs for variable viruses such as influenza (12, 13) , HIV (14, 15) , and RSV (16, 17) where rationally designed immunogens optimize presentation of key conserved epitopes, mask sites using N-glycans, or stabilize conformations or assembly of the envelope glycoproteins. Recent studies have reported use of several of these strategies in the context of HCV glycoproteins, including re.....
Document: There have been a number of successful structure-based vaccine designs for variable viruses such as influenza (12, 13) , HIV (14, 15) , and RSV (16, 17) where rationally designed immunogens optimize presentation of key conserved epitopes, mask sites using N-glycans, or stabilize conformations or assembly of the envelope glycoproteins. Recent studies have reported use of several of these strategies in the context of HCV glycoproteins, including removal or modification of N-glycans to improve epitope accessibility (18, 19) , removal of hypervariable regions (18, 20, 21) , or presentation of key conserved epitopes on scaffolds (22, 23) . However, such studies have been relatively limited compared with other viruses, in terms of design strategies employed and number of designs tested, and immunogenicity studies have not shown convincing improvement of glycoprotein designs over native glycoproteins in terms of neutralization potency or breadth (18, 21) , with the possible exception of an HVR-deleted high molecular weight form of the E2 glycoprotein that was tested in guinea pigs (20) .
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