Electroporation of a multivalent DNA vaccine cocktail elicits a protective immune response against anthrax and plague

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• 作者：Mark T. Albrecht^a ; Brian D. Livingston^b ; ¹ ; John T. Pesce^a ; Matt G. Bell^a ; Drew Hannaman^b ; Andrea M. Keane-Myers^a ; ^{andrea.keane-myers@med.navy.mil}
• 关键词：Anthrax ; Plague ; DNA vaccine ; Recombinant protein vaccine ; Intramuscular electroporation ; Immunization
• 刊名：Vaccine
• 出版年：2012
• 期刊代码：89_0264410x
• 类别：imm
• 出版时间：6 July, 2012
• 卷：30
• 期：32
• 页码：4872-4883
• 文件大小：1122 K

摘要

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-纬 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-纬. 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.