Abstract

The core directed by Drs. de Silva and Miley will provide the following services. 1) Cloning of recombinant dengue protein """"""""constructs for expression (Aim 1 Miley) 2) Cloning of recombinant influenza protein constructs for expression (Aim 1 Miley) 3) Large scale production and purification of dengue antigens from the 4 serotypes (Aim 1 Miley) 4) Large scale production and purification of influenza antigens (Aim 1 Miley) 5) Assessing the structural integrity of recombinant antigens (Aim 1- desilva) 6) Quality control testing of vaccine antigens (Aim 1-Miley) 7) Growth of hybridomas and purification of monoclonal antibodies (Aim 2-Miley) 8) Testing of immune sera for DENV neutralizing antibodies against the 4 serotypes (Aim 3 desilva) 9) Testing the breadth of neutralizing antibody responses using panels of viruses that cover the genetic diversity of each dengue serotype (Aim 3 deSilva)

Public Health Relevance

Dengue is the most significant arboviral infection of humans. Currently there are no vaccines or drugs against this virus. The overall objective of this program is to combine a unique nanoparticle production process with novel innate immune regulators to develop a broad spectrum platform for delivering vaccines against dengue and influenza viruses. This core will provide specific reagents and assays required for developing and evaluating dengue virus vaccines.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program--Cooperative Agreements (U19)
Project #
1U19AI109784-01
Application #
8657217
Study Section
Special Emphasis Panel (ZAI1)
Project Start
Project End
Budget Start
2014-07-01
Budget End
2015-06-30
Support Year
1
Fiscal Year
2014
Total Cost
Indirect Cost

  Institution

Name
University of North Carolina Chapel Hill
Department
Type
DUNS #
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599

  Publications

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

Showing the most recent 10 out of 23 publications