title: A DNA vaccine for venezuelan equine encephalitis virus delivered by intramuscular electroporation elicits high levels of neutralizing antibodies in multiple animal models and provides protective immunity to mice and nonhuman primates.
abstract: We evaluated the immunogenicity and protective efficacy of a DNA vaccine expressing codon-optimized envelope glycoprotein genes of Venezuelan equine encephalitis virus (VEEV) when delivered by intramuscular electroporation. Mice vaccinated with the DNA vaccine developed robust VEEV-neutralizing antibody responses that were comparable to those observed after administration of the live-attenuated VEEV vaccine TC-83 and were completely protected from a lethal aerosol VEEV challenge. The DNA vaccine also elicited strong neutralizing antibody responses in rabbits that persisted at high levels for at least 6 months and could be boosted by a single additional electroporation administration of the DNA performed approximately 6 months after the initial vaccinations. Cynomolgus macaques that received the vaccine by intramuscular electroporation developed substantial neutralizing antibody responses and after an aerosol challenge had no detectable serum viremia and had reduced febrile reactions, lymphopenia, and clinical signs of disease compared to those of negative-control macaques. Taken together, our results demonstrate that this DNA vaccine provides a potent means of protecting against VEEV infections and represents an attractive candidate for further development.
authors: Virology, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, MD 21702-5011, USA. connie.schmaljohn@amedd.army.mil
authors: Lesley C
authors: LC
authors: Dupuy
authors: Michelle J
authors: MJ
authors: Richards
authors: Barry
authors: B
authors: Ellefsen
authors: Lillian
authors: L
authors: Chau
authors: Alain
authors: A
authors: Luxembourg
authors: Drew
authors: D
authors: Hannaman
authors: Brian D
authors: BD
authors: Livingston
authors: Connie S
authors: CS
authors: Schmaljohn
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood*; D000914:Antibodies, Viral / Q000097:blood*; D004195:Disease Models, Animal; D018274:Electroporation; D004666:Encephalitis Virus, Venezuelan Equine / Q000235:genetics / Q000276:immunology*; D004685:Encephalomyelitis, Venezuelan Equine / Q000473:pathology / Q000517:prevention & control*; D005260:Female; D005334:Fever / Q000517:prevention & control; D006023:Glycoproteins / Q000235:genetics / Q000276:immunology; D008231:Lymphopenia / Q000517:prevention & control; D008251:Macaca; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011817:Rabbits; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology; D013997:Time Factors; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology; D014765:Viral Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D014766:Viremia / Q000517:prevention & control
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D006023:Glycoproteins; D011994:Recombinant Proteins; D019444:Vaccines, DNA; D014759:Viral Envelope Proteins; D014765:Viral Vaccines