Vaccines & Vaccination

Biography

Biography: Charani ranasinghe

Abstract

We have shown that the efficacy of a heterologous, poxvirus prime-boost immunization is strongly influenced by the cytokine milieu at the priming vaccination site, where endogenous IL-4/IL-13 is detrimental to the quality of the HIV specific CD8 T cells induced. We have recently developed two novel HIV vaccines that co-express i) IL-13R2 which can transiently inhibit IL-13 activity, and ii) an IL-4R antagonist that can bind to IL-4 type I and II receptors with high affinity, and transiently prevent the signalling of both IL-4 and IL-13 activity at the vaccination site. Following intranasal/intramuscular recombinant fowl pox prime, recombinant Modified Vaccinia Ankara virus booster followed by an gp140 Env protein booster these vaccines were able to induced not only high avidity poly-functional mucosal/systemic gag-specific CD8 T cell immunity but also B cell immunity compared to the unadjuvanted vaccine strategy. Whilst IL-13R2 adjuvanted strategy only induced p55gag-specific IgG1 antibodies, the IL-4R antagonist vaccine was able to induce excellent long-lived p55gag-specific IgG1 and IgG2a antibody differentiation. Moreover, following 3-6 weeks post Env protein booster vaccination only the 13R2 adjuvanted strategy, was able to induce elevated env-IgG1 antibody responses. But, at 16-20 weeks both novel vaccines were able to induce elevated env-specific IgG1 antibody responses of high avidity. Collectively, the IL-4R antagonist adjuvanted vaccine strategy was able to induce excellent triple action CD8 T and B cell (gag & env) immunity, similar to HIV elite controllers and the responders in the RV144 trail, which offer good promise for a future HIV-1 vaccine. This strategy also has high potential as a platform technology against may other chronic mucosal pathogens.