The vast majority of existing vaccines need to be kept cold, a costly and logistical challenge that limits access to millions of people living in poor and wartorn regions. But a new vaccine could surpass these storage limitations.
An experimental combination vaccine for tetanus and diphtheria remains effective when kept out of the fridge for a year or more, researchers report August 5 in Lancet Discovery Science. The team is now investigating whether the technique used for this vaccine can be applied to other vaccines, including those for hepatitis B and HPV.
The new Td vaccine is a repurposed version of a vaccine already approved by the World Health Organization, says biochemist Karen O’Hanlon, the chief operating officer of Stablepharma, the London-based company that created the new vaccine. The data shows that it offers the same efficacy as existing vaccines, she says, adding that the company can confidently extend the shelf life of their fridge-free vaccines to at least 4 years. This would be “significantly longer than any other vaccine product on the market at present,” says O’Hanlon.
Public health agencies including the U.S. Centers for Disease Control and Prevention strictly recommend keeping vaccines at temperatures between 2°Celsius and 8°C from manufacturing until administered. This refrigeration ensures that the delicate biological products do not break down and the vaccine doesn’t lose its potency. But 2. 7 billion people don’t have reliable access to vaccines, in some cases due to destruction of vaccine cold storage equipment and fuel and power outages. This makes it difficult to keep vaccines cool. Fifty percent of vaccines produced globally every year are wasted, in large part because of temperature fluctuations in storage that damage their efficacy.
The World Health Organization makes a few exceptions to the typical cold-storage rules in cases where higher temperatures don’t affect stability. But even in these cases, vaccines typically go without refrigeration for only 3 to 4 days. Freeze-drying can extend a vaccine’s shelf life, and may affect its temperature tolerance. A freeze-dried oral vaccine for rotavirus, for example, can be stored at 25°C for 30 months. But it’s a rare example. The low temperatures created during freeze-drying can also damage vaccine components.
Because of the existing challenges, pediatric immunologist Saul Faust and his colleagues at the National Institute for Health and Care Research in England set out to create a safe and effective vaccine that didn’t need refrigeration. They began with TetaDif—an existing tetanus-diphtheria combination vaccine. The researchers teamed up with Stablepharma, which has a technology called StablevaX that adds inert pharmaceuticals, including the sugar trehalose, to a vaccine’s components before it is freeze-dried. This pharmaceutical assortment forms a protective layer that immobilizes the components and maintains their stability even when temperatures rise. Sterile water is injected into the vaccine before it is used.
The inspiration for using trehalose came from desert plants that can survive years of drought. These plants use trehalose in place of water to maintain the shape of their cells.
In the trial, 60 participants in the United Kingdom ages 18 to 55 who hadn’t received a tetanus or diphtheria vaccine for at least 10 years were injected once with either the new vaccine, called SPVX02, the TetaDif vaccine it was modeled on or another tetanus-diphtheria combination vaccine called diTeBooster.
SPVX02, which was stored at up to 30°C for a year before administration, did not cause any serious side effects. In follow-up examinations 28 days later, scientists found that all SPVX02 recipients had immunity against tetanus and diphtheria toxins that matched that of participants who received the other vaccines.
In separate studies in animals, the new vaccine maintained its potency at 30°C with 75 percent humidity for two years, and at 40°C with 75 percent humidity for six months, meeting temperature tolerance requirements for regions with heat and high humidity. An upcoming trial will further compare the vaccine’s safety and efficacy to TetaDif in 160 people.
Chemical engineer Jennifer Pancorbo from North Carolina State University in Raleigh is pleased to see a possible solution to some of the limitations of freeze-drying and to see that the vaccine produced an immune response equal or better than the standard vaccines.
One current drawback is that the technology cannot be applied to mRNA vaccines, which are stored at as low as -90°C. “These vaccines typically contain lipid nanoparticles which make the freeze-drying part of the manufacturing process difficult to perform,” O’Hanlon says.
