PROJECT REQUIREMENTS The VRC seeks support for manufacture of first generation HIV passive protection candidates including the following elements: Manufacture of multiple bnAbs 1. Stable Cell Line development 2. Process development 3. cGMP manufacturing, including technology transfer, regulatory support, and GLP toxicology Electroporation for Improved Transfections 4. Equipment for research scale evaluation and cell line development using the electroporation process 5. Large scale equipment for product development and cGMP production, including ongoing service contracts and clinical use licensing and fees CHO DG44 Cell Bank 6. Develop cell line and create Master Cell Bank Additional details of these requirements below: Electroporation equipment for rapid transient transfection production and cell line development of HIV vaccine candidates: In collaboration with DAIDS, the VRC has begun work to develop methods for rapid transient transfection production of cGMP grade HIV vaccine candidates. Early data from DAIDS indicates that electroporation could be 5 ? 10 x more productive over current stable cell line-based HIV Env trimer production. This could potentially reduce timelines by several months or improve the productivity of the production process for Phase I HIV vaccine clinical trial. The VRC seeks support for methods for transfection by electroporation, including electroporators for development work at the VRC Vaccine Product Program Laboratory and for pilot cGMP production at the VRC Pilot Plant. Cell Bank of CHO DG44 cells for HIV candidate production: The VRC plans to create a cGMP suitable cell bank of CHO DG44 cells for cell line development and GMP electroporation of HIV vaccine candidates. This non-commercial cell bank would be an available resource for stable cell line development both for VRC products and also for other DAIDS and NIAID initiatives. Non-severable deliverable: cGMP clinical material for Phase 1 Clinical Trial study PROJECT ABSTRACT Advances in the identification of broadly neutralizing antibodies to HIV have raised new opportunities to prevent infection through the administration of antibodies that neutralize diverse strains of the virus. Among these antibodies, an exceptionally broadly neutralizing antibody, VRC01, has been isolated by the Vaccine Research Center, National Institute of Allergy and Infection Diseases, NIH (VRC, NIAID, NIH). VRC01 neutralizes more than 90% of genetically diverse HIV strains by binding to the conserved CD4 binding site of the HIV-1 gp120 envelope.
