Preventative Vaccines for Zika Virus Outbreak: Preliminary Evaluation

Kim, Eun; Erdos, Geza; Huang, Shaohua; Kenniston, Thomas; Falo, Louis D.; Gambotto, Andrea

Although in the presented studies the adenovirus-based Ad5.ZIKV-Efl vaccine was the most potent of the two tested ZIKV vaccine candidates, we acknowledge that is the least likely among the two candidates to be translated into a clinical product. This is because the prevalence of anti-adenovirus serotype 5-neutralizing antibodies in humans limits its use as suitable clinical vaccine platform. However, the experimental use of serotype 5 adenoviral-based vaccines, as shown in this study, is an invaluable tool for the antigen vaccine selection for any given pathogen. Conversely, the MNA-delivered ZIKV vaccine MNA-ZIKV-rEfl, although not optimized for inducing neutralizing immunity in the current format, is a clinically applicable vaccine platform to target infectious diseases such as ZIKV. The geometric design of the MNA-based vaccine platform affords unique advantages for efficient delivery and targeting to the superficial skin microenvironment, which is rich in antigen-presenting cells. While immunogenicity was lower than that observed in a previously reported adjuvented and inactivated whole virus vaccine , the MNA-based vaccine offers the safety and clinical advantages of a defined recombinant subunit antigen and the potential for local co-delivery of adjuvants at very low doses. Co-delivery of TLR ligand adjuvants at very low concentrations can substantially increase the immunogenicity of an influenza subunit vaccine (Weldon et al., 2012) . Importantly, the fabrication process of MNAs affords unique product advantages in reproducibility, safety, manufacturing, and distribution critical for widespread clinical deployment. Thus, our current and future efforts toward the clinical translation of ZIKV vaccine are directed toward the testing and comparison of different E antigen formats (dimeric vs. trimeric), and clinically relevant antigen-adjuvant formats that can be co-delivered in MNAs.