A Randomized Phase I Clinical Trial of HydroVax-YFV, a Novel Inativated Yellow Fever Vaccine

Yellow fever virusYFVis a mosquito borne emerging re emerging hemorrhagic fever virus that causesmortality and is endemic in andgtcountriesThe current live attenuated YFV vaccine was developed inand has proven to be effective at saving millions of lives from this devastating diseaseNeverthelessthis is a live attenuated vaccine that is contraindicated in healthy people who have egg allergies as well as vulnerable populations including young infantspregnant or breastfeeding womenand the elderlyDuring recent outbreaksthese at risk groups have had no alternatives to live yellow fever vaccination and our goal is to produce a vaccine that is safe for both healthy and vulnerable populationsAccording to the CDClive YFV vaccines causeserious adverse eventsSAEper million vaccinationsSAE defined as resulting in hospitalizationlong term disabilityor deathVaccine associated neurological disease occurs at a rate of up tocase pervaccinationsYFV vaccination of infants andltmonths of age has been contraindicated since thes due to excessively high rates of vaccine associated encephalitis in this age groupMore recentlylive YFV vaccination has been contraindicated in breastfeeding mothers due to documented cases of virus transmission via breastmilk to infants who later developed YFV associated neurological disease including seizuresIn patients andgtyears of ageYFV vaccination causes severe viscerotropic disease at an incidence rate of approximatelywith a mortality rate of andgtThe overall mortality rate following YFV vaccinationall agesis estimated attodeaths per million dosesDespite these clear gaps in vaccination coveragethere is currently no commercial vaccine available for these vulnerable populationsTo address this critical unmet needwe have discovered a safe and immunogenic peroxide inactivated yellow fever vaccineHydroVax YFVImportantlythis advanced vaccine is safe and provides complete protection against lethal viscerotropic yellow fever in a robust non human primate modelHerewe propose a double blindrandomizedplacebo controlled Phase I dose escalation trial to evaluate the preliminary safety and immunogenicity of HydroVax YFVOur goal is to eventually expand vaccine coverage to a broader range of patients and the successful completion of this study will represent a key milestone in the advancement of a clinically relevant vaccine against yellow fever and provide a much needed approach to protect the most susceptible members of society including infantselderlyand those with potentially compromised immune functions In this proposalwe provide preclinical data demonstrating the safetyimmunogenicityand protective efficacy of an advanced HydroVax vaccine platform and propose to evaluate the safety and immunogenicity of a novel peroxide inactivated whole virus yellow fever vaccine in a double blind placebo controlled Phase I clinical trial