Electroporation of a multivalent DNA vaccine cocktail elicits a protective immune response against anthrax and plague.
Electroporation of DNA vaccines represents a platform technology well positioned for the development of multivalent biodefense vaccines. To evaluate this hypothesis, three vaccine constructs were produced using codon-optimized genes encoding Bacillus anthracis Protective Antigen (PA), and the Yersinia pestis genes LcrV and F1, cloned into pVAX1. A/J mice were immunized on a prime-boost schedule with these constructs using the electroporation-based TriGrid Delivery System. Immunization with the individual pDNA vaccines elicited higher levels of antigen-specific IgG than when used in combination. DNA vaccine effectiveness was proven, the pVAX-PA titers were toxin neutralizing and fully protective against a lethal B. anthracis spore challenge when administered alone or co-formulated with the plague pDNA vaccines. LcrV and F1 pVAX vaccines against plague were synergistic, resulting in 100% survival, but less protective individually and when co-formulated with pVAX-PA. These DNA vaccine responses were Th1/Th2 balanced with high levels of IFN-γ and IL-4 in splenocyte recall assays, contrary to complimentary protein Alum vaccinations displaying a Th2 bias with increased IL-4 and low levels of IFN-γ. These results demonstrate the feasibility of electroporation to deliver and maintain the overall efficacy of an anthrax-plague DNA vaccine cocktail whose individual components have qualitative immunological differences when combined.
Biological Defense Research Directorate, Naval Medical Research Center, 8400 Research Plaza, Fort Detrick, MD 21702, USA.
Mark T
MT
Albrecht
Brian D
BD
Livingston
John T
JT
Pesce
Matt G
MG
Bell
Drew
D
Hannaman
Andrea M
AM
Keane-Myers
D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000534:Alum Compounds / Q000008:administration & dosage; D000818:Animals; D000881:Anthrax / Q000517:prevention & control; D022122:Anthrax Vaccines / Q000008:administration & dosage* / Q000276:immunology; D000907:Antibodies, Bacterial / Q000097:blood; D000917:Antibody Formation; D018274:Electroporation; D005240:Feasibility Studies; D005260:Female; D007114:Immunization / Q000379:methods*; D007074:Immunoglobulin G / Q000097:blood; D007371:Interferon-gamma / Q000276:immunology; D015847:Interleukin-4 / Q000276:immunology; D051379:Mice; D010930:Plague / Q000517:prevention & control; D010931:Plague Vaccine / Q000008:administration & dosage* / Q000276:immunology; D010957:Plasmids / Q000008:administration & dosage / Q000276:immunology; D013154:Spleen / Q000276:immunology; D058408:Th1-Th2 Balance; D017778:Vaccines, Combined / Q000008:administration & dosage; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000276:immunology
D000276:Adjuvants, Immunologic; D000534:Alum Compounds; D022122:Anthrax Vaccines; D000907:Antibodies, Bacterial; D007074:Immunoglobulin G; D010931:Plague Vaccine; D017778:Vaccines, Combined; D019444:Vaccines, DNA; D015847:Interleukin-4; D007371:Interferon-gamma