Development of a Balanced and Efficacious Live-attenuated Tetravalent Dengue Vaccine

In this proposal, we will further the development of a tetravalent live-attenuated dengue virus vaccine capable meeting the needs of the deploying warfighter, including durable/broad immunity against ALL four serotypes. Codagenix has data demonstrating that our human-codon-deoptimized type-2 DENV strain is: 1) orders of magnitude attenuated; 2) efficacious in mice; and 3) immunogenic in primates. Based on our promising data, we have now synthesized live-attenuated vaccine strains for all four DENV serotypes, which will be tested in primates at NMRC. For this Phase I SBIR we will “re-balance” potential unequal immunogenicity that will be revealed by the efficacy testing of our tetravalent DENV vaccine candidate in primates at NMRC. Because the SAVE platform for DENV vaccine candidate construction is rapid and nimble, producing new versions of two or more serotypes can be accomplished quickly (~14 days). In Option period, we will test stability of our vaccine strains at room and elevated temperature over time to demonstrate that the Codagenix DENV vaccine will satisfy the Army’s need for a stable vaccine for deploying war-fighters. In Phase II , we will prepare the re-balanced tetravalent vaccine for clinical testing via GMP manufacturing and execute a Phase I/II clinical trial in Phase III.