How COVID unlocked the power of RNA vaccines

The technology could revolutionize efforts to immunize against HIV, malaria, influenza and more.

NATURE, 12 JANUARY 2021
Elie Dolgin

Small particles, big advance

Vaccines teach the body to recognize and destroy disease-causing agents. Typically, weakened pathogens or fragments of the proteins or sugars on their surfaces, known as antigens, are injected to train the immune system to recognize an invader. But RNA vaccines carry only the directions for producing these invaders’ proteins. The aim is that they can slip into a person’s cells and get them to produce the antigens, essentially turning the body into its own inoculation factory.

Vaccine manufacturing facilities have had to ramp up their capabilities to produce RNA vaccines.Credit: Robin van Lonkhuijsen/ANP/AFP/Getty

Need for speed

RNA vaccines seem built for speed. From the genetic sequence of a pathogen, researchers can quickly pull out a potential antigen-encoding segment, insert that sequence in a DNA template and then synthesize the corresponding RNA before packaging the vaccine for delivery into the body.

Other treasures

Advances in the technology are now helping researchers to close in on some of the holy grails of vaccine development — such as a universal flu shot that would work against any strain of the virus without being redesigned each year. Others are eyeing jabs against HIV and other top killers in lower-income countries. Such vaccines have eluded scientists often because of the way that pathogens systematically alter their surface proteins to evade immune recognition. Some infectious agents, such as malaria, also have elaborate life cycles that further complicate the process of picking antigens.

Stability and safety

Despite its many potential advantages, today’s RNA-vaccine technology leaves room for improvement. “This technology is still super early,” says Robin Shattock, an immunologist at Imperial College London, “and we’re going to see multiple generations and iterations over the coming years, I suspect.”

In small doses

Unlike the front-runner RNA-based vaccines, which contain little more than the coding sequence for the coronavirus spike protein flanked by regulatory regions on either end, these self-replicating vaccine candidates also include instructions for the RNA to copy itself.

Senior Advisor for Health Care Strategy to BCG — Boston Consulting Group