Presentation: Effect of the Membrane Proximal Region on the Antigenic Structure of Herpes Simplex Virus Glycoproteins gD, gC, and gE

Presented by: Tina Cairns, PhD, Staff Scientist , University of Pennsylvania

Abstract: Herpes simplex virus (HSV) types 1 and 2 contain multiple glycoproteins on its membrane surface to facilitate virus entry, cell-cell spread, and immune evasion. gD is the receptor-binding protein and initiates the virus-cell fusion process. gE is involved in cell-cell spread and works in immune evasion by binding an antibody’s Fc domain. gC is important for virus attachment and inhibits complement activation by binding C3b. Modifications of these three glycoproteins form the basis of an HSV-2 vaccine currently in human trials (BNT163, NCT0543258). We asked whether the inclusion of the membrane proximal region (MPR) of each protein would affect their antigenic properties. We created detailed antigenic maps for soluble forms of gD, gC, and gE, both with and without the MPRs.  Kinetic analysis of the glycoproteins using HT-SPR suggested differences in MAb-gD avidity depending on gD length. In addition, multiple MAbs displayed significant kinetic differences between the gE forms. Our data suggest that the addition of the 14 membrane proximal region residues to gE and 10 residues to gD affect their antigenic structure.