The overarching goal of the work is to develop a DNA vaccine that can be rapidly produced, effectively delivered, and requires fewer doses to elicit long-term protective immunity as compared with current DNA vaccines.
GE Research will create a synthetic DNA vaccine by rolling circle amplification (RCA). This process has the potential to greatly shorten production time while providing higher quantities of clinical grade DNA than can be obtained by typical fermentation methods. Further, the RCA process allows easy assessment of modifications that can enhance immunogenicity.
In addition, we will test a variety of delivery options; ballistic delivery (gene gun) to the skin, which is minimally invasive and has been shown to provide excellent stimulation of immune responses for a variety of DNA vaccines, plus a novel handheld ultrasound delivery technology for topical administration of DNA, and finally a simple intranasal (IN) delivery method that capitalizes on novel RCA DNA modifications.
We will also leverage molecular adjuvants for improving the immunogenicity of the plasmid-based DNA vaccine as well as test novel genetic adjuvant approaches for enhancing the immunogenicity of the RCA DNA vaccine delivered to an animal disease model.
Finally, we will explore receptor-binding fusion technology to create a DNA vaccine which will produce expression products targeted for uptake by immune cells via IN delivery. The end goal is to devise novel DNA design, construction, and delivery strategies that will result in more rapid vaccine production, strong innate and adaptive immune responses in one or two doses, and delivery using less invasive and logistically constrained methods.
While the immediate customer for this effort is the United States Department of Defense, rapid vaccine manufacturing has far-reaching implications for protection against newly emergent infectious disease in any setting. An ideal biodefense vaccine could be designed and cost-effectively manufactured in days to weeks, would have few complex logistical requirements for mass vaccination, and would be able to induce protective immunity in one or two doses. DNA vaccines have the potential to meet all of these objectives. Among all types of vaccines, only DNA-based vaccines can be quickly generated within weeks or even days after first identifying the sequence of an emerging infectious disease threat, a bioterror agent, or even a genetically engineered pathogen. DNA vaccines have been shown to elicit both cellular and humoral immune responses in animal models and to induce protective immunity against a wide range of infectious diseases using only small quantities of DNA.
Capabilities utilized for DNA Vaccine Improvements project
Exploring the physics of ultrasound signal generation, propagation and detection for medical and industrial applicationsRead more
Working from the molecular scale through human health and disease by building novel technology solutions for cell analysis and imaging applicationsRead more