Structure-based design of hepatitis C virus E2 glycoprotein improves serum binding and cross-neutralization

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

While binding to H77 E1E2 resembled binding to H77 sE2, with no apparent difference between immunized groups, we observed notable differences in binding to HCVpps representing H77C, UKNP1.18.1, and J6 for H445P-immunized mice versus mice immunized with wild-type sE2. The difference between J6 HCVpp binding from H445P-immunized mice versus sE2-immunized mice was highly significant (p ï‚£ 0.0001, Kruskal-Wallis test). To confirm this difference in HCVpp binding between sE2 and H445P immunized groups, given the relatively low levels of overall titers, H77C HCVpps were purified and tested in ELISA for binding to pooled sera from sE2 and H445P immunized mice. This confirmed differences between immunized groups for sera from Day 56, as well as Day 42, which corresponds to three rather than four immunizations (Figure 6 ).