Much of the news about vaccines to combat the pandemic emphasizes speed: a “race” to approval, “Operation Warp Speed” and the truly record-breaking timelines. But speed is not the only remarkable aspect of the process that will soon result in vaccines reaching tens of millions of Americans. The first two vaccines, from Pfizer and Moderna, rely on an extraordinary advance in technology, never before used on such a scale, with great promise for the future, and some uncertainties.
In the past, vaccines were largely based on an inactivated or weakened form of a pathogen that was used to train the body’s immune system to fight an infection. Such vaccines have been remarkably successful in fighting diseases such as measles and polio, but they have also taken many years and sometimes decades to develop.
By contrast, the pair of new vaccines rely on a tiny piece of synthesized genetic material known as messenger RNA. In nature, mRNA serves to convey instructions inscribed in DNA and deliver them to the protein-making parts of a cell. The new vaccines use the synthesized mRNA to deliver instructions to the cell to produce the spike protein that the coronavirus uses to latch on to a cell and infect it. When the spike proteins are produced by the cell — on instruction from the mRNA — they then train the body’s immune system to go after them.
Reaching this point is the culmination of many years of work by scientists, often outside the limelight. Scientists have known since 1961 about mRNA, but exploiting it for medicine was a complex task. One of the early problems was that, when injected, it could cause an inflammatory reaction. But Katalin Kariko and Drew Weissman, working at the University of Pennsylvania, figured out in 2005 how to modify the mRNA so that the body did not react with inflammation, overcoming a key hurdle and paving the way for today’s vaccines. A second hurdle that vexed scientists was how to fortify the fragile mRNA particles for delivery to the cell. The solution was to encase it in small bubbles of fat known as lipid nanoparticles.
One of the most promising outcomes of the research is the development of nucleic acid-based “platforms” that may be reused to design vaccines for different diseases, starting as soon as the genetic sequence of a pathogen is known, and also using processes that are scalable and reproducible for rapid response to an outbreak.
Clinical trials suggest that the vaccines are safe and provide protection from COVID-19, but longer-term monitoring of those who get the vaccine is essential. How long will the immunity last? Are there unknown side effects, in particular for people with immune system disorders? Fortunately, other vaccines using more traditional methods also are nearing readiness. Given the catastrophic scope of the pandemic, every vaccine that works will be needed, down to the very last dose.
