Cytolytic Perforin as an Adjuvant to Enhance the Immunogenicity of DNA Vaccines

Shrestha, Ashish C.; Wijesundara, Danushka K.; Masavuli, Makutiro G.; Mekonnen, Zelalem A.; Gowans, Eric J.; Grubor-Bauk, Branka

A chimeric version of the oligomerization domain from the chicken complement inhibitor (C4bp) was used to produce an oligomeric form of vaccine antigens [35, 83] . This protein, termed IMX313, forms a heptameric structure of the vaccine protein. This has been used to develop DNA vaccines for tuberculosis, malaria and HIV to enhance humoral and/or cellular responses [35, 36, 84] . Vaccination with a DNA vaccine encoding secreted HIV Tat (TPA-Tat IMX313) induced higher humoral and cellular responses and improved protection against EcoHIV challenge in mice [36] . A phase I clinical trial of tuberculosis vaccine MVA85A-IMX313 evaluated the vaccine to be safe and immunogenic, but cellular (Ag85A-specific IFN- [81] . The proposed mechanism of HSP70 as an adjuvant is that TLR 2/4 on DCs interacts eted or bound HSP70, further attracting DCs to the site of antigen expression. This is by DC maturation, presentation of antigens by MHC molecules and secretion of cytokines mulatory molecules [82] , thus enhancing T cell immune responses against the vaccine en Complement Inhibitor imeric version of the oligomerization domain from the chicken complement inhibitor as used to produce an oligomeric form of vaccine antigens [35, 83] . This protein, termed forms a heptameric structure of the vaccine protein. This has been used to develop DNA for tuberculosis, malaria and HIV to enhance humoral and/or cellular responses [35, 36, 84] . on with a DNA vaccine encoding secreted HIV Tat (TPA-Tat IMX313) induced higher and cellular responses and improved protection against EcoHIV challenge in mice [36] . A inical trial of tuberculosis vaccine MVA85A-IMX313 evaluated the vaccine to be safe and enic, but cellular (Ag85A-specific IFN-Ƴ ) and humoral (MVA-specific IgG) responses were ficant [85] . Thus, the ability of such an adjuvant to enhance immunogenicity of DNA n humans is still debated.