The overall objective of Project 3 is to coordinate the effort in manufacturing, quality control, and quality assurance of the vaccine components and final vaccine formulation under GMP, organize and oversee the conduct of GLP-level definitive toxicology, biodistribution and integration studies, and finally, deliver a stability tested and FDA reviewed candidate vaccine product for a Phase 1 safety and immunogenicity study to be conducted at NIH's HIV Vaccine Trial Network (HVTN).
Aim 1. To manufacture DNA vaccine components and produce final formulation under cGMP conditions. To conduct appropriate release testing according to DNA vaccine specifications for bulk and vialed DNA vaccine materials.
Aim 2. To manufacture protein vaccine components and produce final formulations under cGMP conditions. To conduct appropriate release testing according to protein vaccine specifications for bulk and vialed materials. To purchase and formulate a GMP-grade adjuvant as part of the protein boost formulation.
Aim 3. To conduct definitive toxicology studies to evaluate the safety of the next generation DNA prime - protein boost HIV-1 vaccine formulation including a new adjuvant. In addition, the biodistribution/integration of a single-dose administered DNA vaccines will be evaluated under cGLP conditions.
Aim 4. To establish Project Management-based operation and control procedures for the coordination of al Project 3 activities including interactions among the different elements of this IPCAVD program and interactions between our program and subcontractors related to the vaccine manufacturing and toxicology studies.
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|Marty-Roix, Robyn; Vladimer, Gregory I; Pouliot, Kimberly et al. (2016) Identification of QS-21 as an Inflammasome-activating Molecular Component of Saponin Adjuvants. J Biol Chem 291:1123-36|
|Costa, Matthew R; Pollara, Justin; Edwards, Regina Whitney et al. (2016) Fc Receptor-Mediated Activities of Env-Specific Human Monoclonal Antibodies Generated from Volunteers Receiving the DNA Prime-Protein Boost HIV Vaccine DP6-001. J Virol 90:10362-10378|
|Suschak, John J; Wang, Shixia; Fitzgerald, Katherine A et al. (2016) A cGAS-Independent STING/IRF7 Pathway Mediates the Immunogenicity of DNA Vaccines. J Immunol 196:310-6|
|Pan, Ruimin; Chen, Yuxin; Vaine, Michael et al. (2015) Structural analysis of a novel rabbit monoclonal antibody R53 targeting an epitope in HIV-1 gp120 C4 region critical for receptor and co-receptor binding. Emerg Microbes Infect 4:e44|
|Zhang, Lu; Wang, Wei; Wang, Shixia (2015) Effect of vaccine administration modality on immunogenicity and efficacy. Expert Rev Vaccines 14:1509-23|
|Suschak, John J; Wang, Shixia; Fitzgerald, Katherine A et al. (2015) Identification of Aim2 as a sensor for DNA vaccines. J Immunol 194:630-6|
|Buglione-Corbett, Rachel; Pouliot, Kimberly; Marty-Roix, Robyn et al. (2014) Reduced MyD88 dependency of ISCOMATRIX™ adjuvant in a DNA prime-protein boost HIV vaccine. Hum Vaccin Immunother 10:1078-90|
|Pouliot, Kimberly; Buglione-Corbett, Rachel; Marty-Roix, Robyn et al. (2014) Contribution of TLR4 and MyD88 for adjuvant monophosphoryl lipid A (MPLA) activity in a DNA prime-protein boost HIV-1 vaccine. Vaccine 32:5049-56|
|Hollister, Kristin; Chen, Yuxin; Wang, Shixia et al. (2014) The role of follicular helper T cells and the germinal center in HIV-1 gp120 DNA prime and gp120 protein boost vaccination. Hum Vaccin Immunother 10:1985-92|
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