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.

Keywords:

• DNA vaccine
• ebola virus
• electroporation
• filovirus
• codon-optimized
• marburg virus

Disclosure of Potential Conflicts of Interest

D.H. is Vice President, Research and Development of Ichor Medical Systems. H.A.V is employed by Integrated BioTherapeutics, Inc. K.L.W. was formerly Vice President, Vaccine Development, for Integrated BioTherapeutics, Inc. C.S.S, J.W.H, and Ichor Medical Systems have a variety of ongoing collaborative research and development agreements for vaccine development. The authors declare no other competing interests.

Acknowledgments

The authors thank Joshua Moore, James Fiallos, Darrell Wetzel, Eugene Blue, and William Agee for performing the sample collection and blinded animal health assessments in BSL-4. Further, the authors thank Dr. Jason Goetzman for his coordination of the vaccinations at NIRC; LTC Bridget S. Lewis, LTC Paul R. Facemire, and LTC Shelley Honnold for pathology support (USAMRIID); Dr. Scott Marshall (BioStat Solutions, Inc.) and Dr. Samuel P. Dickson (USAMRIID) for statistical analysis; and Angela Silva, Audra Gravatt, and Stephanie McNulty (The Geneva Foundation) for administrative support.

Funding

The studies described here were supported by Grant Number U01AI082069 from the National Institute of Allergy And Infectious Diseases. Production of the EBOV challenge stock used here was funded by the Joint Program Executive Office for Chemical and Biological Defense, Medical Countermeasures Systems Joint Project Management Office. Opinions, interpretations, conclusions, and recommendations contained within this presentation are those of the authors and are not necessarily endorsed by the United States Army, the National Institute of Allergy and Infectious Diseases, or the National Institutes of Health.

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