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

HCVpp, J6 HCVpp), as well as two mice in the sE2 group and one mouse in the ΔHVR1-Y632NS group (UKNP1.18.1 HCVpp). P-values between group endpoint titer values were calculated using Kruskal-Wallis analysis of variance with Dunn's multiple comparison test, and significant pvalues between sE2 control and sE2 design groups are shown (*: p  0.05; **: p  0.01; ****: p  0.0001). The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.04.15.044073 doi: bioRxiv preprint Serum dilutions were performed as two-fold dilutions starting at 1:64, and minimum dilution levels (corresponding to 1:64) are indicated as dotted lines for reference. Murine sera with low (ID50 < 10) or incalculable ID50 values due to low or background levels of neutralization (observed only for some mice for J6 HCVpp neutralization) have ID50 shown as 10. Due to insufficient sera, J6 neutralization measurements did not include two mice from group 1 (sE2) and one mouse from group 4 (ΔHVR1). P-values between group ID50 values were calculated using Kruskal-Wallis analysis of variance with Dunn's multiple comparison test, and significant p-values between sE2 control and sE2 design groups are shown (*: p  0.05; **: p  0.01). author/funder. All rights reserved. No reuse allowed without permission.