Advanced Preclinical Testing of a Novel Recombinant Vaccine Against Zika Virus

PROJECT SUMMARY ABSTRACT The recent acceleration in incidence and intensity of human disease caused by Zika virusZIKVinfection has prompted an international outcry for safe and effective countermeasuresCurrently protection against mosquito bites and vector control are the only measures available to prevent ZIKV infectionsA vaccine is urgently neededThe studies proposed here build on previous work that demonstrates the protective efficacy of recombinant vaccines using the Modified Vaccinia AnkaraMVAlive viral vectorGeoVax has constructed two novel MVA vaccine candidates against ZIKVone expressing the ZIKV NSproteinand a second expressing ZIKV prMEBoth vaccine candidates show excellent immunogenicity and protective efficacy against ZIKV infection in a stringent intracerebral challenge mouse modelIn this applicationwe propose to evaluate the immunogenicity and protective efficacy of these two vaccine candidates in rhesus macaquesRMThe project has three specific aimsUnder the first aimGeoVax will scale up vaccine production for a large study in RM and develop methods for quality control and standardization of methods for vaccine preparationUnder the second aimRM will be immunized with the two vaccines following either a prime only or a prime boost vaccination regimenSamples will be collected from the immunized animals at discrete intervals and tested for antigen specific antibody by ELISAfor neutralizing antibody by PRNTand for antigen specific T cell responses by flow cytometry of cells stained by intracellular cytokine staining for activation of CDand CDpopulationsThe protective efficacy of these vaccines in RM will be tested by challenging the immunized animals with live ZIKV and assessing viral load in serum and other tissues compared to the sham immunized control groupUnder the third aim we will investigate the role of antibody in protection using passive transfer experiments in micePurified IgG from sera of immunized RM will be passively transferred to mice that will then be challenged with appropriate ZIKV strains and assessed for temporal viremia following intravenous challengeAdditionallywe will test RM immune sera and controls for potential antibody dependent enhancement of infectionADEusing Dengue serotypeas a modeland for the presence of autoantibodies that react with self antigensThe vaccine candidate yielding optimal protection with minimal detrimental effects will be chosen for further developmentThe long term objective of this project is clinical development and testing of vaccine candidates against ZIKV infectionin response to aNIAID call to the research community highlighting its interest in funding such researchUpon completion of this two year projectGeoVax will submit a Phase II SBIR to request funding for further development of the selected vaccine candidate in preparation for human clinical testing