Engineering Nanoparticle Alum Adjuvants for Pandemic Influenza Vaccines

Project Summary SignificanceSinceavian influenza AH Nhas sickened overpeople with amortality rateHalf of all cases occurred inwhich also saw the emergence of a highly pathogenic strainThusH Navian influenza is poised to emerge as a devastating pandemic in a worldwide population that has no pre existing immunityCurrent Hvaccineswhether attenuatedinactivatedsplit or recombinantare insufficiently immunogenic in peopleAddition of adjuvants including squalene emulsions or alum can improve the immunogenicity of Hvaccinesbut these adjuvanted vaccines still require two immunizations to achieve protective antibody titers and these responses are not durableAdditionallyit is unknown if these adjuvanted vaccines provide sufficient breadth of immunity to be effective against the antigenically drifted Hstrains which have begun to appearThus there is an urgent need to develop a more effective and safe adjuvant for Hinfluenza vaccines to meet these shortcomingsImproving the adjuvanticity of a clinically approved alum adjuvant by optimizing its structure and composition is an under explored solution to this important challengeInnovationThe physical properties of adjuvants affect their ability to induce a robust immune responseFor examplereducing the particle size of alum fromtom tonm generates a stronger immune response while decreasing injection site inflammationAdditionallysurface charge affects adjuvant uptake in vivo and determines the binding affinity of vaccine antigens to alumWe have taken advantage of this knowledge to generate an exciting new class of adjuvantsstable and well defined aluminum nanoparticlesnanoalumusing a unique and scalable method to produce stable nanoparticles from the clinically approved alumA prototype nanoalum demonstrates superior adjuvant activity compared to Alhydrogel and augments the efficacy of an experimental flu vaccineSpecific AimsIn Phase I of this SBIR we will complete two specific aimssynthesize stable nanoalum formulations that are compatible with an HVLP antigen andidentify the nanoalum properties that augment the safe and durable protective immunity to H NvirusesIn Phase II will complete preclinical efficacy and safety testingprocess developmentand GMP manufacture in preparation for clinical testing Narrative SinceH Navian influenza has infected more thanpeople in China and killed approximatelymaking it the most likely flu virus to cause a worldwide pandemic if it achieves sustained human to human transmission in world wide population that has no pre existing immunity to HCurrent Hvaccines require two doses to produce protective immunity in peopleyet protective immunity does not persist for very long with these vaccinesthese vaccines are less immunogenic in older populationsand it is unknown if the current vaccines will be protective against the newer variants of H Nthat are emergingWe have developed a novel class of nanoparticle alum adjuvants to enhance vaccine activity which we propose to optimize to augment the efficacy vaccines to prevent an Hinfluenza pandemic