Improving the pharmacokinetics, potency, and immunogenicity of eCD4-Ig

PROJECT SUMMARY We have developed an antibody like HIVentry inhibitoreCDIgcomposed of the first two domains of CDfused to an antibody Fc domain and a short tyrosine sulfated CCRmimetic peptideeCDIg has properties that make it an exceptionally promising tool in the fight against the HIVpandemicSpecificallyit is broader than any broadly neutralizing antibodybNAbat least as potent at neutralization and antibody dependent cell mediated cytotoxicityADCCmore difficult to escapeless immunogenicand uniquely capable of amplifying the ADCC activity of non neutralizing antibodies in patient seraWhen expressed by an adeno associated virusAAVvectorit can protect rhesus macaques from SHIV and SIV challenges more effectively than any conventional vaccine strategyandas we show hereit can suppress viral rebound after cessation of combined antiretroviral therapiescARTIn shortthe case for optimizing eCDIg is strongHere we describe a series of cell culture and animal studies that will further extend eCDIg s half lifeimprove its potencyand reduce its immunogenicityThese improvements will increase the safety and efficacy of eCDIg as an infused protein and as an AAV expressed transgeneand bring us closer to our goals of sustained drug free HIVremission and effective long term prophylaxis against HIVinfection PROJECT NARRATIVE eCDIg is an exceptional HIVentry inhibitor that may help prevent new HIVinfections and maintain a drug free state of HIVremission in infected personsHere we will extend its half lifeincrease its neutralization potencyand reduce its immunogenicitythereby improving its safetyefficacyand cost