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 codonoptimized 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-g 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.

DNA vaccines 2014 meeting: Highlights and overview

“…Ebola and Marburg virus. In the interesting study by Grant-Klein entitled "Codon-optimized filovirus DNA vaccines delivered by intramuscular electroporation protect cynomologous macaques from lethal Ebola and Marburg virus challenges" demonstrates considerable protection from infection by Ebola and Marburg virus challenge in monkeys which were vaccinated by electroporation mediated delivery, with plasmids expressing the glycoprotein antigens from these two filoviruses 13 . In the paper by Valentin et.…”

Ebola virus vaccines – reality or fiction?

“…DNA vaccines have been shown to induce cellular as well as humoral immune responses, but regularly require administration of several doses to achieve the desired immunity [27]. While DNA vaccines have shown some efficacy in ZEBOV rodent models [28, 29], the efficacy of ZEBOV GP in NHPs has yet to reach 100% with a recent report describing codon optimized DNA vaccines providing 83% protection against ZEBOV challenge [30]. …”

Advancements in DNA vaccine vectors, non-mechanical delivery methods, and molecular adjuvants to increase immunogenicity

“…Improved delivery technologies, such as intramuscular or intradermal electroporation, have been used to facilitate transport of DNA into cells, resulting in much better immunogenicity in both clinical and non-clinical studies. [13][14][15][16][17][18][19] In one study, electroporation-enhanced DNA vaccination resulted in increased polyfunctional antigen-specific CD8 C T cells in patients receiving a HPV DNA vaccine expressing the E6 and E7 genes of HPV16 and HPV18 respectively. 20 The majority of DNA vaccinated patients displayed complete regression of their cervical lesions, as well as viral clearance, following DNA delivery.…”