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An adjuvant for an RSV prefusion F vaccine that safely protects infants via maternal vaccination
Phone: (631) 235-9297
Phone: (917) 806-4057
A Respiratory Syncytial VirusRSVvaccine is not yet availableAvatar is developing a noveldi tyrosine crosslinkedconformationally locked preF subunit immunogenDT preFthatformulated with an adjuvantwill form the basis of a preF RSV vaccineThe risk of vaccine enhanced diseaseVEDcame into sharp focus with the results of as formalininactivated RSV vaccine that resulted in numerous hospitalizations and the deaths of two childrenA maternalto infant vaccination strategy using a potent immunogen is therefore now considered the safest and most promising strategy for protecting infantsWe have developed a maternal to infant vaccination mouse model that uses a highly virulent subtype of RSV lineand is uniquely able to elicit immune responses and pathology in mice that mirror many of the fundamentalage dependent characteristics of enhanced RSV disease observed in humansThe model can distinguish between safe and unsafe vaccine immunogen formulationsand using this this model enables us to identify a DT preF adjuvant formulation that overcomes the risks of VEDIn Phase I of this proposalwe will test four DT preF adjuvant formulations and identify the one that elicits the most protective responses that does not cause VED in vaccinatedpregnant dams or non pregnant female miceor lead to the development of enhance respiratory diseaseERDin infant mice born to immunized mothersfollowing RSV challengeIn Aim Iwe will rank and select the two most potent DT preF adjuvant formulationsbased on neutralization titersin immunizedadult female micein Aim IIwe will identify a lead DT preF adjuvant formulation that most effectively protects postpartum damsnewborn pups and weanlings following maternal vaccinationbased on lung viral titersand in Aim IIIwe will demonstrate that our DT preF adjuvant formulation elicits protective responses that do not lead to the development of ERD in dams or infant mice following RSV challengeIn Phase IIwe will carry out additional preclinical studies in cotton rats as the next step toward human clinical studies Our lead formulation will be innovative in that it willihave sufficient stability for commercial developmentiiprovide infants safepotentlong lastingand cost effective protection against RSVandiiienable maternalto infant vaccination There is currently no effective vaccine for RSVand each yearRSV infectsmillion children in the US and is the leading cause of infant hospitalizationsGloballyit accounts forof deaths in infantssecond only to malariaand in addition it poses a serious threat to the elderly and immuno compromisedWe propose to test adjuvant formulations with our RSV vaccine immunogena recombinant soluble F fusion protein stabilized in its prefusion conformationthat will trigger the production of antibodies in vaccinated individuals that will bind toand neutralize the virus when it enters the bodyWe will select an adjuvant that enhances the potency of our immunogenand that modulates immune responses to avoid any safety risks!
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