With the recent announcement that two RNA vaccines are more than 90 percent effective against COVID-19, vaccinology has taken one of the largest technological leaps in nearly a century. But after the initial euphoria that we may get some relief from the still growing COVID-19 pandemic, enthusiasm chilled with the recognition that these vaccines would need to be kept either frozen or deep-frozen for a significant portion of their distribution.
The need for a cold chain has severely complicated efforts to get effective vaccines to people in both wealthy countries like the United States, but also the poorest corners of the globe. Fortunately, solutions have been developed to allow these promising vaccines to be stored and delivered at room temperature — we urgently need to prioritize these strategies to end the COVID-19 pandemic.
The new RNA vaccines deliver a piece of genetic information from the SARS-CoV-2 virus into human cells so those cells can make innocuous viral proteins to which the human immune system can respond. The viral genes are encoded in RNA, a molecule that is inherently unstable outside the safe environment of a cell and can be destroyed by enzymes in the environment that are less active at ultra-cold temperatures. To protect the RNA, it is placed inside a “ball of fat” that delivers it safely to the inside of the cell. These nanoparticles are also unstable at warm temperatures; much like butter, they melt. While the technology is extraordinarily promising, it is not designed for the warmer temperatures of conventional refrigerators, doctor’s offices, pharmacies and especially not the elevated temperatures seen in many resource-limited parts of the world.
Most vaccines are sensitive to temperature extremes. If the vaccine is too warm, it degrades, and if it is too cold, the freezing temperatures can destroy it. Several studies over the past two decades have found that up to one-third of vaccines are exposed to temperatures outside the recommended range, and this did not differ substantially between rich and poor countries. A U.S. Office of the Inspector General report in 2012 found that up to three-quarters of provider offices failed to maintain vaccines purchased for children with government funds in the United States at proper temperatures. Taken together, even with the extreme efforts the companies developing RNA vaccines have undertaken to invest in cold storage and distribution in the U.S., COVID-19 vaccines may be rendered less effective by temperature excursions. And it is likely that low and middle-income countries will struggle to support such a robust cold chain infrastructure.
Fortunately, solutions already exist for this problem, but we need to prioritize a diversity of approaches, as no one will be appropriate for all settings. The strategy that has received most attention has been the massive investment in technologies to store and deliver cold vaccines. Pfizer reportedly has spent $2 billion on a distribution network for its heat-sensitive RNA vaccine, outside of the government’s Operation Warp Speed. In addition to the substantial logistical hurdles to make this feasible, it does little to support cold-chain capacity more broadly in the U.S. and nothing for those in other parts of the world. Individual states have also made large investments in “deep freezer farms;” these are challenging and costly to maintain, and may be quickly rendered obsolete if there are no other infectious disease vaccines built on heat-sensitive RNA technologies in the near future.
Clever inventions have been made over the last several years to keep vaccines cold, even in hot, resource-limited settings. But these devices either are still in early phases or have not been engineered to sustain the deep cold required for today’s RNA vaccines. Perhaps most promising are advances in molecular biology and biochemistry that allow RNA vaccines to be stable at warmer temperature. The German company, CureVac, packs RNA in its COVID-19 vaccine tightly, putatively protecting it from the environment and allowing it to be stable at simply refrigerator temperatures for months. At Infectious Disease Research Institute (IDRI), we have developed techniques to freeze dry vaccine components, including RNA and the nanoparticles used to deliver it. We have demonstrated that this technology will allow our COVID-19 RNA vaccine to be effective after nearly a year at room temperature, and up to two years with simple refrigeration. While we are still taking this vaccine through the development pipeline, our technology can rapidly be applied to existing RNA vaccines shown to be effective in Operation Warp Speed.
The more than $10 billion given to large pharmaceutical companies from the U.S. Government to facilitate COVID-19 vaccines in Operation Warp Speed has allowed for a number of promising vaccine options in record time. We now need to make smaller, rapid and creative investments in the non-profit, academic and startup biotech sectors that are working on advancing RNA vaccine technologies so that the every person in the United States and around the world can have immediate access to the most effective vaccines for COVID-19 irrespective of their zip or country code. It would be a tragedy to develop successful vaccines for COVID-19 that leave sizable numbers of people out in the cold.
Corey Casper, MD, MPH, is the chief executive officer at the Infectious Disease Research Institute (IDRI) and clinical professor of medicine and global health at the University of Washington.