Impact of Ebola Mucin-Like Domain on Antiglycoprotein Antibody Responses Induced by Ebola Virus-Like Particles

• Published in: The Journal of infectious diseases Vol. 204; no. suppl_3; pp. S825 - S832
• Main Authors: Martinez, Osvaldo, Tantral, Lee, Mulherkar, Nirupama, Chandran, Kartik, Basler, Christopher F.
• Format: Journal Article
• Language: English
• Published: United States Oxford University Press 01.11.2011
• Subjects: Animals; Antibodies; Antibodies, Viral - biosynthesis; CHO Cells; Cricetinae; Cricetulus; Crimean-Congo hemorrhagic fever virus; Dendritic cells; Disease Models, Animal; Ebola virus; Ebolavirus - immunology; General practice; Glycoproteins; Glycoproteins - immunology; Hemorrhagic Fever, Ebola - immunology; Hemorrhagic Fever, Ebola - virology; Humans; Infections; Mice; Monoclonal antibodies; Neutralizing antibodies; Plasmids; Protein Structure, Tertiary; Vaccines, Virus-Like Particle - immunology; Vesicular stomatitis virus; VIRAL BIOLOGY; Viral Proteins - immunology; Viruses
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1093/infdis/jir295

Ebola virus (EBOV) glycoprotein (GP), responsible for mediating host-cell attachment and membrane fusion, contains a heavily glycosylated mucin-like domain hypothesized to shield GP from neutralizing antibodies. To test whether the mucin-like domain inhibits the production and function of anti-GP antibodies, we vaccinated mice with Ebola virus-like particles (VLPs) that express vesicular stomatitis virus G, wild-type EBOV GP (EBGP), EBOV GP without its mucin-like domain (ΔMucGP), or EBOV GP with a Crimean-Congo hemorrhagic fever virus mucin-like domain substituted for the EBOV mucin-like domain (CMsubGP). EBGPVLP immunized mice elicited significantly higher serum antibody titers toward EBGP or its mutants, as detected by western blot analysis, than did VLP-ΔMucGP. However, EBGP-, AMucGP-and CMsubGP-VLP immunized mouse sera contained antibodies that bound to cell surface-expressed GP at similar levels. Furthermore, low but similar neutralizing antibody titers, measured against a vesicular stomatitis virus (VSV) expressing EBGP or ΔMucGP, were present in EBGP, ΔMucGP, and CMsubGP sera, although a slightly higher neutralizing titer (2-to 2.5-fold) was detected in ΔMucGP sera. We conclude that the EBOV GP mucin-like domain can increase relative anti-GP titers, however these titers appear to be directed, at least partly, to denatured GP. Furthermore, removing the mucin-like domain from immunizing VLPs has modest impact on neutralizing antibody titers in serum.