The purpose of this contract is to identify several cellular factors that have a major impact on production of a full-length HIV-1 envelope trimer without altering its native antigenic properties.

million adults and more thanchildren become infected with HIV each yearAn effective HIV vaccine is a one time intervention that is extremely cost effective compared with the cost of lifelong treatmentThe classical vaccination approaches that have been successful in the control of various viral diseases by priming the adaptive immunity to recognize the viral envelope proteins have failed in the case of HIVOne of the reasons is that the epitopes of the viral envelope are more variable than those of many other virusesFurthermorethe functionally important epitopes of the gpprotein are masked by glycosylationtrimerisation and receptor induced conformational changes making it difficult to block with neutralising antibodiesOne approach to this challenge is to create a single peptide that contains the least variable components of all the known HIV strainsWe are currently working on this approach with the support from NIH NIAIDRRto identify an HIV gpprotein with such charactersAnother road block is the yield of HIV envelope protein which often is on the order of mg L compared to mAbs at gm LOur goal in this proposal is to establish an expression system to maximize production of the full length HIVEnv spikes with native antigenic propertiesTo complete this projectwe willover express the cellular factors that may promote Env productionknock down the cellular factors that may impede Env productionBy the end of Phase I of this proposalwe expect to identify several cellular factors that have a major impact on production of a full length HIVEnv trimer without altering its native antigenic properties