R01FD007456

A novel first-in-class 3D printing technology for advanced manufacturing of complex vaccine formulations against influenza and emerging infectious diseases - project summary:

Vaccination is known to be the most effective strategy to manage the spread and deleterious impact of various infectious diseases including the most recent emerging, Coronavirus Disease 2019, COVID-19.

Recombinant protein subunit vaccines have demonstrated promising results for immunization against infectious diseases recently. These vaccines are manufactured through recombinant DNA technology in which the gene fragment that encodes the production of the recombinant protein is introduced to a host cell as an expression system.

The genetically engineered cells can proliferate and produce a high amount of the protein of the target which can be separated and purified in the succeeding steps.

The recent progress in genetic tool development to manipulate the microorganisms and utilization of mammalian cell lines in biopharmaceutical manufacturing have projected the global protein markets to reach $228.4 billion by the end of this year.

However, this industry is still overloaded with processes that lack flexibility and process controls or integration needed for continuous or on-demand production capacity.

There is no biomanufacturing system that can produce recombinant proteins through a single-step continuous manufacturing process. So, due to the high demand for vaccines all over the world, there’s an immense need for highly efficient yet inexpensive technologies.

Yeast expression systems such as Pichia pastoris (P. pastoris) can be used as an expression host cell which offers numerous advantages over traditional systems including high growth rate, easy genetic manipulation process, high yield protein expression, performing eukaryotic post-translational modifications, appropriate protein folding and protein secretion in the external medium, and easy purification process.

In this project, we will utilize a novel sprayed multi adsorbed-particle reposing technology (SMART) 3D printing technique to produce biocompatible Pluronic (F127)-bisurethane methacrylate (F127-BUM) polymers based microcarrier immobilized with P. pastoris which can be used in large-scale fermentations for production of recombinant proteins.

Our SMART technology meets the requirements for recombinant proteins manufacturing such as ease of scale-up, correct protein folding, and short post-production processing. It also has the potential to improve agility, flexibility, cost, and robustness in the manufacturing processes for complex protein-based biologics.

Additionally, in contrast to other particulate fabrication techniques, SMART can incorporate live cells during the single-step microparticle formulation process.

This technology can easily host further ancillary processes such as ultra-low temperature freezing print bed (-80°C or lower), fiber optic probes for the inline monitoring of critical product quality attributes (CQAs) such as viscosity, content uniformity, and stability, making it accessible to industry in the near term with a robust control strategy.

Our SMART will be implemented in a continuous setup to manufacture dry powder bioengineered P. pastoris encapsulated F127-BUM microcarriers to produce recombinant proteins for infectious diseases such as vaccines against Epstein-Barr virus (EBV) and influenza vaccines.

The University Of Mississippi

TO ASSIST INSTITUTIONS AND ORGANIZATIONS, TO ESTABLISH, EXPAND, AND IMPROVE RESEARCH, DEMONSTRATION, EDUCATION AND INFORMATION DISSEMINATION ACTIVITIES, ACQUIRED IMMUNODEFICIENCY SYNDROME (AIDS), BIOLOGICS, BLOOD AND BLOOD PRODUCTS, THERAPEUTICS, VACCINES AND ALLERGENIC PROJECTS, DRUG HAZARDS, HUMAN AND VETERINARY DRUGS, CLINICAL TRIALS ON DRUGS AND DEVICES FOR ORPHAN PRODUCTS DEVELOPMENT, NUTRITION, SANITATION AND MICROBIOLOGICAL HAZARDS, MEDICAL DEVICES AND DIAGNOSTIC PRODUCTS, RADIATION EMITTING DEVICES AND MATERIALS, FOOD SAFETY AND FOOD ADDITIVES. THESE PROGRAMS ARE SUPPORTED DIRECTLY OR INDIRECTLY BY THE FOLLOWING CENTERS AND OFFICES: CENTER FOR BIOLOGICS EVALUATION AND RESEARCH (CBER), CENTER FOR DRUG EVALUATION AND RESEARCH (CDER), CENTER FOR DEVICES AND RADIOLOGICAL HEALTH (CDRH), CENTER FOR VETERINARY MEDICINE (CVM), CENTER FOR FOOD SAFETY AND APPLIED NUTRITION (CFSAN), NATIONAL CENTER FOR TOXICOLOGICAL RESEARCH (NCTR), THE OFFICE OF ORPHAN PRODUCTS DEVELOPMENT (OPD), THE CENTER FOR TOBACCO PRODUCTS (CTP), AND OFFICE OF REGULATORY AFFAIRS (ORA), AND THE OFFICE OF THE COMMISSIONER (OC). SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAMS: TO STIMULATE TECHNOLOGICAL INNOVATION, TO ENCOURAGE THE ROLE OF SMALL BUSINESS TO MEET FEDERAL RESEARCH AND DEVELOPMENT NEEDS, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION BY MINORITY AND DISADVANTAGED PERSONS IN TECHNOLOGICAL INNOVATION. FUNDING SUPPORT FOR SCIENTIFIC CONFERENCES THAT ARE RELEVANT TO THE FDA SCIENTIFIC MISSION AND PUBLIC HEALTH ARE ALSO AVAILABLE.

93.103 - Food and Drug Administration Research

FDA Office of Acquisition and Grant Services (OAGS) [HHS - FDA]

Center for Biologics Evaluation and Research (CBER) [HHS - FDA]

University, Mississippi 386771848 United States

Single Zip Code

Enhancing Innovations in Advanced Manufacturing Technologies for Vaccines against Influenza and Emerging Infectious Diseases (R01) Clinical Trials Not Allowed (RFA-FD-21-033)

Amendment Since initial award the End Date has been extended from 08/31/24 to 08/31/25 and the total obligations have increased 200% from $498,189 to $1,495,036.