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

Different cytokines, such as interleukins (IL-2, IL-6, IL-12), chemokines, granulocyte/macrophage colony-stimulating factor (GM-CSF), costimulatory molecules (CD40, CD80, and CD86), and signaling molecules (Interferon regulatory factor -3) have been used as genetic adjuvants with DNA vaccines [39, 40, [42] [43] [44] 48, 68] . Genes expressing IFN-γ IL-2, IL-12, IL-15, and IL-18 have been used to stimulate Th1 responses [44, 45, 70] , and IL-4, IL-6, IL-10, IL-13, for Th2 stimulation [42, 43, [71] [72] [73] . The inclusion of genes encoding cytokines, like IL-2 or IL-12, as adjuvants for HIV-1 DNA vaccines is known to increase cell mediated immunity (CMI) [74, 75] . However, a bicistronic HIV DNA encoding gp120 and IL-2 elicited weaker specific immune response than monocistronic HIV-1 gp120 DNA [76] . Combinations of genetic adjuvants like IL-2 and IL-15 with HIV-1 DNA vaccine have also been used but no synergistic effect on the level of total antibody to HIV-1 antigen was reported [77] . A phase I/IIa trial showed that coadministration of DNA vaccine encoding prostatic acid phosphatase (PAP) with GM-CSF elicited PAP-specific CD4 + and/or CD8 + T cell responses [68] . However, GM-CSF was administered as a recombinant protein.