PNAS First Look Blog

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Making vaccines not need refrigeration

Left) The genetically modified viral protein; the inserted peptides are marked with a blue arrow. (Middle) The viral particle. The blue areas represented the inserted peptides. (Right) The viral particle, with the grey shell representing a layer of calcium phosphate. Credit: R. Tang et al., PNAS.

Left) The genetically modified viral protein; the inserted peptides are marked with a blue arrow. (Middle) The viral particle. The blue areas represented the inserted peptides. (Right) The viral particle, with the grey shell representing a layer of calcium phosphate. Credit: R. Tang et al., PNAS.

Millions of deaths happen each year from vaccine-preventable diseases because vaccines break down from heat and developing countries often lack ways to properly refrigerate them. Now researchers suggest eggshell-like coatings can make vaccines more thermally stable.

Vaccines against polio, smallpox, measles, yellow fever and many other diseases have protected billions worldwide for decades. However, more than 17 million deaths caused by infectious diseases still happen every year, accounting for about a quarter of all deaths worldwide, and most of these are caused by vaccine-preventable diseases. The problem is “most vaccines must be constantly refrigerated, and many communities lack electricity, especially in the poorest countries,” says chemist Ruikang Tang at Zhejiang University in Hangzhou, China.

Keeping vaccines refrigerated can be difficult and expensive—the “cold chain” from production to use of vaccines consumes about 80 percent of the total cost of vaccination programs. “An estimated 151 million vaccine doses delivered to developing countries spoiled without proper refrigeration in 2007,” Tang says.

Tang investigates biomineralization—how life can produce mineral structures. “I noticed that different from other living cells, eggs have mineral shell structures so they can be stored at room temperature for weeks,” he says.

Much as clothes help people adapt to environments, “it was reasonable to prepare ‘clothes’ for cells,” Tang says. He and his colleagues have successfully coated yeast and zebrafish embryos in protective mineral shells, and investigated whether or not the same could hold true for vaccines.

Tang and his colleagues experimented with a vaccine strain of human enterovirus type 71, a relative of polio, hepatitis A, and foot-and-mouth disease. They genetically modified it to generate peptides on its surface that helped it produce a calcium-rich eggshell-like coating.

“We had selected many peptides for tests but most of them did not work—most modified proteins could not be assembled into viral particles anymore,” Tang says. “We needed great patience to keep on trying.”

This self-biomineralized vaccine can be stored at 26 degrees C for more than nine days and at 37 degrees C for approximately one week. Experiments in live mice showed this vaccine was still useful for vaccinations—the shell likely spontaneously degrades after the vaccine enters cells. “This kind of thermostable vaccine can be produced in a low price,” says researcher Cheng-Feng Qin at the Beijing Institute of Microbiology and Epidemiology. The scientists detailed their findings online April 15 in the Proceedings of the National Academy of Sciences.

The researchers hope to further improve the vaccine’s thermal stability through more precise and protective mineral coatings. “Our aim is to store vaccines at room temperature for months,” Tang says. “Thus, the expensive cold chain can be completely removed from vaccination programs.” Qin notes “the first vaccine product may be a thermostable polio vaccine, which is urgently needed in Africa.”

Categories: Applied Biological Sciences | Pharmacology
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