With the goal of developing a thermostable tuberculosis vaccine that is resistant to damage from excessive heat or cold, IDRI (Infectious Disease Research Institute) today announces it has been awarded a contract from the National Institute of Allergy and Infectious Diseases, a part of the National Institutes of Health. The contract (HHSN272201400041C) has a base award of $3.6 million and could be worth up to $11.9 million if all milestone-driven options are exercised. The contract provides funding for a team of IDRI scientists – led by Christopher Fox, PhD – to develop, produce and test a thermostable lyophilized formulation of its vaccine candidate to prevent tuberculosis. TB-causing bacteria infect an estimated one-third of the global population, and, in 2013, approximately nine million people developed active cases of TB illness.
"You can have the best vaccine in the world, but if it's damaged during the delivery process, it does no good," says Steven G. Reed, PhD, IDRI president, founder and chief scientific officer. "Thermostable vaccines could have great economic and health benefits for the recipients by ensuring that vaccines are intact and effective when delivered."
According to experts from Doctors Without Borders, the need to maintain vaccines in a temperature-controlled supply chain – known as the "cold chain" – all the way to the patient is one of the biggest barriers to effective vaccination, particularly for the last stretch to reach the most remote areas. Vaccines lose potency over time, with the rate of potency loss related to temperature; most currently used vaccines have a shelf life of two years or longer only if they are continuously stored at refrigerated conditions of 36-46 degrees Fahrenheit.
"Too often in vaccine development, the question of deliverability isn't asked until it's too late in the process," says Fox, director of IDRI's Adjuvant Formulations Program. "We are nimble enough that we can get in the door with a new process early in the development cycle that addresses this issue, including the added challenge that comes with lyophilizing vaccines containing complex multi-component formulations."
Next-generation, rationally designed vaccines such as IDRI's TB vaccine contain both an antigen (a non-infectious piece of a pathogen that the immune system learns to attack) and an adjuvant (substances added to vaccines to enhance the ability of antigens to stimulate the body's immune response). However, the two components are often kept in separate vials that must be mixed in exact proportions just in advance of the vaccine being administered, and the cold-chain process must be maintained for long-term stability.
The process of lyophilizing – or freeze-drying -- a vaccine increases its shelf life and addresses the issue of maintaining the cold chain. This could allow vaccines to be shipped throughout the world without being hampered by the necessity of a continuous cold chain or separate antigen/adjuvant vials.
IDRI is building upon the success of its current TB vaccine efforts. IDRI's vaccine component, ID93 (which consists of a recombinant fusion of four TB antigens), has recently completed a Phase 1 clinical trial demonstrating good safety at different doses in healthy adult volunteers. IDRI's adjuvant component, GLA-SE, was evaluated together with ID93 as a liquid mixture in the same clinical trial at two different adjuvant doses, maintaining a good safety profile.
"To provide the foundation for our product development plan for this contract, IDRI conducted successful preliminary studies showing that ID93 and GLA-SE can be co-lyophilized to generate a single-vial dried vaccine that maintains protective biological activity even after exposure to 122 degrees Fahrenheit for one month," says Fox. The results of those preliminary studies were published in the Journal of Controlled Release earlier this year. "The ultimate test will be completing a Phase 1 clinical trial that shows safety and immunogenicity of a lyophilized adjuvanted vaccine."
According to Fox, the result of this contract will be the first clinical emulsion-based adjuvant formulation to be successfully lyophilized. "To our knowledge, no one has demonstrated being able to lyophilize an oil-in-water emulsion-based adjuvant that maintains the same physicochemical properties after reconstitution as it had before lyophilization so this will be a new step in creating temperature stable vaccines for the future," he said.
IDRI's partners for this contract include Lyophilization Technology, Inc., a contract development and manufacturing organization (CDMO) which provides lyophilization services for development of healthcare products.