This project is focused on the development of a unique GMP-compliant particle molding technology that we have pioneered called PRINT? (Particle Replication in non-wetting templates) as a delivery platform for particulate multivalent vaccines targeting influenza and Dengue viruses. PRINT provides complete control over particle size, shape and chemical composition, and enables the systematic tailoring of antigen proximity to the particle, antigen density and particle size and shape to screen and identify the optimal particle parameters to elicit enhanced immunological responses. The down-selected particle parameters will provide design rules to manufacture influenza and dengue particulate multivalent vaccines to investigate the ability to generate a complete and robust neutralizing antibody response to each antigen. Also, additional Projects within our Program will utilize these multivalent particulate vaccines to address the use of novel adjuvants to modulate the immune response. These particulate vaccines will be evaluated in a humanized mouse model to determine how to prevent infection of homotypic or all 4 dengue virus serotypes. We will combine the learning from each Project to scale-up the most promising multivalent particulate vaccines and advance these to large animal challenge studies for both influenza and dengue. Due to the immediate medical need for multivalent vaccines for influenza and dengue and the cGMP-compliant nature of our particle molding technology, the formulations can be advanced into product development for human trials.
This project will employ a novel, cGMP-compliant nanoparticle molding technology that we have pioneered to develop multivalent vaccines against influenza and dengue virus. Utilizing the unique plug and play capabilities of our process to incorporate and mix and match known anitgens, we will be able to adapt our findings to tailor particulate vaccines to protect against emerging or re-emerging infectious disease.
|Cheng, Liang; Wang, Qi; Li, Guangming et al. (2018) TLR3 agonist and CD40-targeting vaccination induces immune responses and reduces HIV-1 reservoirs. J Clin Invest 128:4387-4396|
|Metz, Stefan W; Thomas, Ashlie; Brackbill, Alex et al. (2018) Nanoparticle delivery of a tetravalent E protein subunit vaccine induces balanced, type-specific neutralizing antibodies to each dengue virus serotype. PLoS Negl Trop Dis 12:e0006793|
|Chen, Naihan; Gallovic, Matthew D; Tiet, Pamela et al. (2018) Investigation of tunable acetalated dextran microparticle platform to optimize M2e-based influenza vaccine efficacy. J Control Release 289:114-124|
|Collier, Michael A; Junkins, Robert D; Gallovic, Matthew D et al. (2018) Acetalated Dextran Microparticles for Codelivery of STING and TLR7/8 Agonists. Mol Pharm 15:4933-4946|
|Cheng, Ning; Watkins-Schulz, Rebekah; Junkins, Robert D et al. (2018) A nanoparticle-incorporated STING activator enhances antitumor immunity in PD-L1-insensitive models of triple-negative breast cancer. JCI Insight 3:|
|Chen, Naihan; Johnson, Monica M; Collier, Michael A et al. (2018) Tunable degradation of acetalated dextran microparticles enables controlled vaccine adjuvant and antigen delivery to modulate adaptive immune responses. J Control Release 273:147-159|
|Metz, Stefan W; Thomas, Ashlie; White, Laura et al. (2018) Dengue virus-like particles mimic the antigenic properties of the infectious dengue virus envelope. Virol J 15:60|
|Shao, Wenwei; Earley, Lauriel F; Chai, Zheng et al. (2018) Double-stranded RNA innate immune response activation from long-term adeno-associated virus vector transduction. JCI Insight 3:|
|Junkins, Robert D; Gallovic, Matthew D; Johnson, Brandon M et al. (2018) A robust microparticle platform for a STING-targeted adjuvant that enhances both humoral and cellular immunity during vaccination. J Control Release 270:1-13|
|Swanson, Karen V; Junkins, Robert D; Kurkjian, Cathryn J et al. (2017) A noncanonical function of cGAMP in inflammasome priming and activation. J Exp Med 214:3611-3626|
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