Chemically Programmable Virus-Like-Particles (cpVLP) for Single Dose Vaccination
Abstract
Vaccines fail because they 1) lack the correct antigen and 2) they don’t induce a sufficient immune response. To address these gaps, our laboratory is in the 1st Option Period of a 3 year DTRA contract entitled “Using Whole Proteome Microarrays to Identify QFever Vaccine Antigen Candidates Associated with Protection. Project CBM-V-01” (HDTRA1-16-C-0009). We use a proteome microarray containing all 2000 proteins from the Q fever agent Coxiella burnetii to discover better vaccine antigens, and novel multi-TLR agonist conjugates to boost immune responses. This project uses a 2 dose, Prime & Boost immunization regimen. In response to the DTRA Topic G11 announcement “Critical Requirements for Effective Single Dose Vaccine”, we will construct and screen an assortment of nanoparticulate and biodegradable microsphere formulations with different physical properties that release antigen and TLR agonists at different rates. By mixing nanoparticles and biodegradable microspheres with different antigen release kinetics we aim to accomplish the Prime & Boost after a single injection. The nanoparticles are also designed to target antigen to the draining lymph node for improved vaccine efficacy. We will use diverse resources and personnel from our institution to accomplish the objectives of this new multidisciplinary proposal. Novel TLR agonists formulated in liposomes, nanoparticles and microspheres will be synthesized in the chemistry department. Vaccine formulations will be developed and characterized in the Pharmaceutical Sciences, Biomedical Engineering, and Chemistry Departments. Advanced immunoimaging resources in our Stem Cell Research Center will be used to determine bioavailability and track delivery of vaccine into the draining lymph node. Immunogenicity studies will be conducted in the Institute for Immunology and Flow Cytometry Facility. Our model vaccine antigen for this project is from Coxiella burnetii a biological weapon. We will utilize an in vivo mouse Immunogenicity Pipeline to evaluate the intensity and duration of the adaptive T- and B-cell mediated immune responses induced by these cpVLPs. Live rodent challenge studies will be conducted in our certified BSL3 animal laboratory that has been registered with the Select Agent program for over 10 years and houses the National Training Center for Select Agent Research.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jul 16, 2019
- Source ID
- HDTRA11810035
Entities
People
- Philip L. Felgner
Organizations
- Defense Threat Reduction Agency
- University of California, Irvine