Researchers from Northwestern and Cornell Universities have produced a platform that can be freeze-dried to create inexpensive, portable, expedited conjugate vaccines, aiming to circumvent a years-long, multimillion-dollar manufacturing process that often results in inequitable distribution.
Their study, published Wednesday in Science Advances, explains that the novel platform, termed iVax, can be freeze-dried and reactivated with just a drop of water. iVax, or “in vitro conjugate vaccine expression,” generates on-demand conjugate vaccines that are cell-free at an extremely rapid rate without compromising the medication.
While the technology is groundbreaking, it will not apply to the mRNA-based COVID-19 vaccine due to a difference in mechanisms.
“Currently, our system can make conjugate vaccines at relevant doses in one hour for less than $1,” said Michael Jewett, a professor of chemical and biological engineering at Northwestern and director of the university’s Center for Synthetic Biology.
Including all expenses, iVax can offer one dose for around $6, the paper says, compared with between $9.50 and $118 for a standard conjugate vaccine dose.
“We think iVAX is going to make a big impact in the way we produce medicines," Jewett told The Academic Times. "Our manufacturing platform doesn't require large centralized facilities and refrigerated supply chains. This should increase our ability to distribute protein medicines, especially in resource-limited settings."
According to the World Health Organization, over 50% of vaccines are wasted by transportation errors globally, and Jewett notes that at least 30% of the world's population is still without access to essential medications.
Conjugate vaccines protect against life-threatening bacterial infections and typically require living cells as a component because their mechanism is based on bacterial cell mechanics. These living cells are pathogens with an external layer of a sugar unique to them. Once the vaccine is injected, the body’s immune system is activated by the sugar attaching to a carrier protein that is already present within the body. If the body ever encounters this sugar again, its immune system will already have been prepared to respond because of the initial immune response catalyzed by the vaccine.
To avoid deterioration of living cells in standard conjugate vaccines, the vaccines must be refrigerated and meticulously monitored prior to and during deployment. Errors in temperature regulation during distribution and storage result in losing the crucial pathogen within the vaccine, making it unusable.
However, “iVAX allows one to make a medicine when and where it is needed,” Jewett said.
Jewett’s cell-free method still uses all of the necessary cell mechanics, but without the living cell itself.
Jewett and his team worked out a way to remove a cell wall and extract the molecular machinery within. This machinery is then freeze-dried and remains shelf-stable for at least six months, until it's exposed to a drop of water. At that point, the water sets off a chemical reaction to reinvigorate the medication, the study says.
To confirm viability of this synthetic cell, the researchers simulated the full process by exposing mice vaccinated through the iVAX method to the fatal pathogenic bacterium Francisella tularensis. According to the research, all vaccinated mice survived.
“Given recent and broad interest in making biomedicine on-demand, we anticipate that this work will provide a transformative approach to promote better access to life-saving vaccines through decentralized production,” Jewett said.
Highlighting the reasoning behind his team’s choice to focus on conjugate vaccines, Jewett emphasized that there is a growing concern of antibiotic resistance, saying that it is like a “slow COVID-19,” meaning it is just as worrying as the pandemic, but acting at a slower rate. Antibiotic resistance will threaten up to 10 million lives per year by 2050, he continued, and conjugate vaccines will be the solution for drug-resistant bacteria as their prevalence increases. Even today, conjugate vaccines are consistently represented in the top-10-selling drugs worldwide.
Although these vaccines do not directly apply to COVID-19, the pandemic has shed light on difficulties with regard to vaccine creation and distribution, illuminating the need for better and more accessible methods. With developing nations and rural areas facing shortages of the vaccine, as well as the costly nature of vaccine manufacturing, Jewett believes that this technology will reach far and wide.
“State-of-the-art manufacturing approaches limit access to conjugate vaccines due to centralized production and cold-chain distribution requirements,” he said. “These requirements represent major technical challenges in vaccination, presenting barriers to the eradication of disease by limiting the reach of vaccination campaigns and slowing response to pathogen outbreaks. iVAX holds promise to address these issues and save lives.”
The article “On-demand biomanufacturing of protective conjugate vaccines” was published Feb. 3 in Science Advances. The authors of the study were Jessica C. Stark, Jasmine M. Hershewe, Karen J. Hsu, Katherine F. Warfel, Rachel S. Dubner and Michael C. Jewett, Northwestern University; Thapakorn Jaroentomeechai, Taylor C. Stevenson, Tyler D. Moeller and Matthew P. DeLisa, Cornell University; and Bridget S. Moricz, Anthony M. Martini and Bradley D. Jones, University of Iowa. The lead author was Michael C. Jewett.