Ebolavirus Glycoprotein (GP), responsible for mediating host-cell attachment and membrane fusion, contains a heavily glycosylated mucin-like domain believed to “shield" GP from neutralizing antibodies. To test whether the mucin domain inhibits the production and function of anti-GP antibodies, we vaccinated mice five times with Ebola virus-like particles (VLPs) that express one of four glycoproteins; wild-type ebolavirus GP (EBGP), ebolavirus GP without its mucin-like domain (ΔMucGP), vesicular stomatitis virus G, and ebolavirus GP with a Crimean-Congo Hemorrhagic Fever Virus mucin domain substituted for the ebolavirus mucin-like domain (CMsubGP). Antibody in sera harvested from EBGP-, ΔMucGP- and CMsubGP-VLP immunized mice demonstrated similar binding against EBGP and its mutants when surface-expressed on CHO-K1 cells. However, significantly higher serum antibody titers from EBGP-VLP immunized mice as compared to VLP-ΔMucGP mouse sera were detected by western blot analysis of EBGP or its mutants. Neutralization assays are being performed to further characterize VLP-immunized mouse sera.