title: Codon-optimized filovirus DNA vaccines delivered by intramuscular electroporation protect cynomolgus macaques from lethal Ebola and Marburg virus challenges.
abstract: Cynomolgus macaques were vaccinated by intramuscular electroporation with DNA plasmids expressing codon-optimized glycoprotein (GP) genes of Ebola virus (EBOV) or Marburg virus (MARV) or a combination of codon-optimized GP DNA vaccines for EBOV, MARV, Sudan virus and Ravn virus. When measured by ELISA, the individual vaccines elicited slightly higher IgG responses to EBOV or MARV than did the combination vaccines. No significant differences in immune responses of macaques given the individual or combination vaccines were measured by pseudovirion neutralization or IFN-γ ELISpot assays. Both the MARV and mixed vaccines were able to protect macaques from lethal MARV challenge (5/6 vs. 6/6). In contrast, a greater proportion of macaques vaccinated with the EBOV vaccine survived lethal EBOV challenge in comparison to those that received the mixed vaccine (5/6 vs. 1/6). EBOV challenge survivors had significantly higher pre-challenge neutralizing antibody titers than those that succumbed.
authors.affiliation: a United States Army Medical Research Institute of Infectious Diseases ; Fort Detrick , MD USA.
authors.forename: Rebecca J
authors.initials: RJ
authors.lastname: Grant-Klein
authors.forename: Louis A
authors.initials: LA
authors.lastname: Altamura
authors.forename: Catherine V
authors.initials: CV
authors.lastname: Badger
authors.forename: Callie E
authors.initials: CE
authors.lastname: Bounds
authors.forename: Nicole M
authors.initials: NM
authors.lastname: Van Deusen
authors.forename: Steven A
authors.initials: SA
authors.lastname: Kwilas
authors.forename: Hong A
authors.initials: HA
authors.lastname: Vu
authors.forename: Kelly L
authors.initials: KL
authors.lastname: Warfield
authors.forename: Jay W
authors.initials: JW
authors.lastname: Hooper
authors.forename: Drew
authors.initials: D
authors.lastname: Hannaman
authors.forename: Lesley C
authors.initials: LC
authors.lastname: Dupuy
authors.forename: Connie S
authors.initials: CS
authors.lastname: Schmaljohn
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D003062:Codon; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D018274:Electroporation; D004797:Enzyme-Linked Immunosorbent Assay; D058501:Enzyme-Linked Immunospot Assay; D005260:Female; D016563:Filoviridae / Q000235:genetics / Q000276:immunology*; D006023:Glycoproteins / Q000235:genetics / Q000276:immunology; D019142:Hemorrhagic Fever, Ebola / Q000517:prevention & control*; D007074:Immunoglobulin G / Q000097:blood; D007273:Injections, Intramuscular; D007371:Interferon-gamma / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008252:Macaca fascicularis; D008297:Male; D008379:Marburg Virus Disease / Q000517:prevention & control*; D009500:Neutralization Tests; D010957:Plasmids; D016019:Survival Analysis; D016896:Treatment Outcome; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D003062:Codon; D006023:Glycoproteins; D007074:Immunoglobulin G; D019444:Vaccines, DNA; D007371:Interferon-gamma
keywords: DNA vaccine; codon-optimized; ebola virus; electroporation; filovirus; marburg virus