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.

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
Name
University of North Carolina Chapel Hill
Department
Type
DUNS #
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599
Metz, Stefan W; Gallichotte, Emily N; Brackbill, Alex et al. (2017) In Vitro Assembly and Stabilization of Dengue and Zika Virus Envelope Protein Homo-Dimers. Sci Rep 7:4524
Junkins, Robert D; Gallovic, Matthew D; Johnson, Brandon M et al. (2017) A robust microparticle platform for a STING-targeted adjuvant that enhances both humoral and cellular immunity during vaccination. J Control Release 270:1-13
Cheng, Liang; Zhang, Zheng; Li, Guangming et al. (2017) Human innate responses and adjuvant activity of TLR ligands in vivo in mice reconstituted with a human immune system. Vaccine 35:6143-6153
Kai, Marc P; Brighton, Hailey E; Fromen, Catherine A et al. (2016) Tumor Presence Induces Global Immune Changes and Enhances Nanoparticle Clearance. ACS Nano 10:861-70
DeSimone, Joseph M (2016) Co-opting Moore's law: Therapeutics, vaccines and interfacially active particles manufactured via PRINT®. J Control Release 240:541-543
Metz, Stefan W; Tian, Shaomin; Hoekstra, Gabriel et al. (2016) Precisely Molded Nanoparticle Displaying DENV-E Proteins Induces Robust Serotype-Specific Neutralizing Antibody Responses. PLoS Negl Trop Dis 10:e0005071
Fromen, Catherine A; Rahhal, Tojan B; Robbins, Gregory R et al. (2016) Nanoparticle surface charge impacts distribution, uptake and lymph node trafficking by pulmonary antigen-presenting cells. Nanomedicine 12:677-687
Callaway, Justin B; Smith, Scott A; Widman, Douglas G et al. (2015) Source and Purity of Dengue-Viral Preparations Impact Requirement for Enhancing Antibody to Induce Elevated IL-1? Secretion: A Primary Human Monocyte Model. PLoS One 10:e0136708
Callaway, Justin B; Smith, Scott A; McKinnon, Karen P et al. (2015) Spleen Tyrosine Kinase (Syk) Mediates IL-1? Induction by Primary Human Monocytes during Antibody-enhanced Dengue Virus Infection. J Biol Chem 290:17306-20
Robbins, Gregory R; Roberts, Reid A; Guo, Haitao et al. (2015) Analysis of human innate immune responses to PRINT fabricated nanoparticles with cross validation using a humanized mouse model. Nanomedicine 11:589-99

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