Mixing virus-based vaccines with sugars and allowing them to dry on a simple filter can keep them stable for four months, even at tropical temperatures. The process, developed and tested by scientists at Nova Bio-Pharma Technologies and the University of Oxford, could provide an inexpensive way to streamline vaccine storage and delivery, reduce waste, and improve vaccine efficacy. “It is very simple,” says Matt Cottingham, a virologist who worked on the project at Oxford.
The new technique could make vaccines cheaper and more accessible in areas lacking modern infrastructure. Existing live vaccines must be refrigerated between 4 °C to 8 °C to remain effective. In countries like England and the United States, maintaining this “cold chain” costs up to $200 million a year and increases the cost of vaccination by 14 percent to 20 percent, according to the World Health Organization. In poor countries, the refrigerated transports and even electricity at medical clinics is often missing altogether, making vaccination impossible.
Nova has previously shown that the technique can stabilize various types of vaccines, as well as protein-based drugs. The new study, published in today’s issue of Science Translational Medicine, is the first time a live-virus vaccine has been kept potent after exposure to high temperatures.
The scientists used the technique on two viruses that are the basis for some of the latest vaccines in development. To make vaccines from these live viruses, the researchers disable the viruses so they can infect a cell in the body but not replicate, and then engineer them to carry genes for proteins from different disease organisms. This way, the viral vaccine will stimulate an immune response but won’t make the recipient sick. The team at the Jenner Institute in Oxford, led by professor Adrian Hill, has pioneered the use of these viruses as the basis for vaccines against tuberculosis, malaria, and a “universal” flu vaccine, as well as for HIV. All of these are currently in clinical trials.
The viruses must remain alive in order to be effective, but they are sensitive to heat. Drying them in the sugar solution makes them less vulnerable. “This could be a really big breakthrough,” says Stephanie James, director of science and director of the Grand Challenges in Global Health Initiative at the Foundation for the National Institutes of Health, which oversaw funding of the work. “These viral vaccine vectors are being seriously examined for the development of a lot of new vaccines to address disease problems that we don’t have vaccines for yet.”
The Oxford team showed that it could preserve the two vaccine viruses by mixing the viruses with sucrose–common table sugar–and trehalose, a sugar found in plants and mushrooms and used as a stabilizer in processed foods. The team then dripped the mixture onto a membrane made of glass fibers and dried it at room temperature in a low-humidity chamber. This allowed the sugars to form a noncrystalline solid around the fibers of the membrane, immobilizing the virus so that nothing could interact with it. Cottingham notes that neither using sugars nor drying are new ways to stabilize pharmaceuticals. “The crucial step is that the drying happens on the membrane, so we can remove the water at a relatively low temperature,” he says. The exact concentrations of sugars and the type of filter used had to be established by trial and error. “There was a pretty big empirical element in all this,” says Cottingham.
To release the vaccine, the researchers flushed the membranes with saline, which dissolves the sugar almost instantaneously. Based on tests done in mice, the team found that they could store the two different vaccines on sugar-stabilized membranes at a tropical 45 °C for as long as six months without any degradation. The vaccines could be kept for over a year and more at body temperature–37 °C–with only tiny losses in effectiveness.
Nova Bio-Pharma holds the patent on the drying technique, and it has also developed a small, plastic cartridge into which the filter is sealed. The cartridge has a hole at either end, one of which fits a sterile syringe and the other a disposable needle. When the vaccine is administered, a nurse or technician would pass sterile saline through the cartridge, pushing it out slowly. This instantly rehydrates the vaccine.
Samodh de Costa, the stabilization project manager at Nova, says the company already has an aseptic manufacturing process in place that can produce quantities that would be needed for clinical trials. The next steps are to show that the process can be scaled up to industrial manufacturing levels and demonstrate that it works with a standard or newly licensed human vaccine.