title: Comparison of the protective efficacy of DNA and baculovirus-derived protein vaccines for EBOLA virus in guinea pigs.
abstract: The filoviruses Ebola virus (EBOV) and Marburg virus (MARV) cause severe hemorrhagic fever in humans for which no vaccines are available. Previously, a priming dose of a DNA vaccine expressing the glycoprotein (GP) gene of MARV followed by boosting with recombinant baculovirus-derived GP protein was found to confer protective immunity to guinea pigs (Hevey et al., 2001. Vaccine 20, 568-593). To determine whether a similar prime-boost vaccine approach would be effective for EBOV, we generated and characterized recombinant baculoviruses expressing full-length EBOV GP (GP(1,2)) or a terminally-deleted GP (GPa-) and examined their immunogenicity in guinea pigs. As expected, cells infected with the GPa- recombinant secreted more GP(1) than those infected with the GP(1,2) recombinant. In lectin binding studies, the insect cell culture-derived GPs were found to differ from mammalian cell derived virion GP, in that they had no complex/hybrid N-linked glycans or glycans containing sialic acid. Despite these differences, the baculovirus-derived GPs were able to bind monoclonal antibodies to five distinct epitopes on EBOV GP, indicating that the antigenic structures of the proteins remain intact. As a measure of the ability of the baculovirus-derived proteins to elicit cell-mediated immune responses, we evaluated the T-cell stimulatory capacity of the GPa- protein in cultured human dendritic cells. Increases in cytotoxicity as compared to controls suggest that the baculovirus proteins have the capacity to evoke cell-mediated immune responses. Guinea pigs vaccinated with the baculovirus-derived GPs alone, or in a DNA prime-baculovirus protein boost regimen developed antibody responses as measured by ELISA and plaque reduction neutralization assays; however, incomplete protection was achieved when the proteins were given alone or in combination with DNA vaccines. These data indicate that a vaccine approach that was effective for MARV is not effective for EBOV in guinea pigs.
authors.affiliation: Department of Molecular Virology, Virology Division, Division U.S. Army Medical Research Institute of Infectious Diseases, 1301 Ditto Ave., Ft. Detrick, Frederick 21702, MD, USA.
authors.forename: Jenny L
authors.initials: JL
authors.lastname: Mellquist-Riemenschneider
authors.forename: Aura R
authors.initials: AR
authors.lastname: Garrison
authors.forename: Joan B
authors.initials: JB
authors.lastname: Geisbert
authors.forename: Kamal U
authors.initials: KU
authors.lastname: Saikh
authors.forename: Kelli D
authors.initials: KD
authors.lastname: Heidebrink
authors.forename: Peter B
authors.initials: PB
authors.lastname: Jahrling
authors.forename: Robert G
authors.initials: RG
authors.lastname: Ulrich
authors.forename: Connie S
authors.initials: CS
authors.lastname: Schmaljohn
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D016367:Baculoviridae / Q000235:genetics / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology; D029043:Ebolavirus / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D006168:Guinea Pigs; D019142:Hemorrhagic Fever, Ebola / Q000517:prevention & control*; D006801:Humans; D009500:Neutralization Tests; D014611:Vaccination; D019444:Vaccines, DNA / Q000276:immunology*; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology; D014765:Viral Vaccines / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D019444:Vaccines, DNA; D014759:Viral Envelope Proteins; D014765:Viral Vaccines; C113189:envelope glycoprotein, Ebola virus