Eight world-renowned scientists, known for their contributions to the development of messenger RNA (mRNA) vaccines gathered for a panel at the Beckman Center of the National Academies of Sciences & Engineering to discuss the future of the technology and what it took to get there on Friday, April 29.
“The COVID vaccine’s success is the result of the conference of two technologies: synthesized mRNA and lipid nanoparticles,” said the organizers of the event.
MRNA is the code inside cells that allows our DNA to be translated into essential proteins, while lipid nanoparticles are small fat molecules that are able to encase foreign mRNA to better get it into our cells.
The scientists in the panel were responsible for technologies that created the mRNA vaccines. Dr. Pieter Cullis, professor of biochemistry and molecular biology at the University of British Columbia, studies ionizable lipids which allow efficient delivery of mRNA code into cells. Dr. Ian MacLachlan, the founder of Protiva Biotherapeutics, pioneered the use of lipid nanoparticles for the delivery of messenger RNA in COVID-19 vaccines. Dr. Drew Weissman, professor of medicine and director of vaccine research with the infectious diseases division in the department of medicine at the University of Pennsylvania, developed technology that enabled stable mRNA. Dr. Barney S. Graham, former deputy director of vaccine research at the National Institutes of Health (NIH) developed a mutation method to stabilize vaccine targets. Dr. Jason McLellan, professor at the University of Texas at Austin, collaborated with Dr. Graham to target stabilized spike proteins.
Prior to the recent advent of the mRNA vaccines, vaccines for illnesses like the flu, chickenpox and measles were made through killed pathogens or weakened live pathogens. Pathogens are any foreign invaders in the human body that can cause illness. Killed pathogens activate your immune system against the pathogen when the immune system recognizes it as foreign material. Weakened pathogen vaccines, or attenuated vaccines, are made by introducing the human disease into an animal where the pathogen will evolve to better work in non-human populations. When the virus or bacteria is put in vaccines it is not optimized for humans anymore and is much easier for our immune system to defend against. These vaccines can present unique manufacturing problems due to how they are produced. mRNA vaccines sought to solve these problems.
“It takes one egg for every dose of flu vaccine. And so you need at least 200 million eggs [per] seasonal vaccine…” UCI director of vaccine research and development, Dr. Philip Felgner said. “But now, we don’t even need a virus… to produce this vaccine. You just need chemicals and some enzymes. It’s a…very big transition in the manufacturing process”
MRNA vaccines work by introducing sections of mRNA that encode for proteins found on the outside of pathogens, in this case, COVID-19, to our own cells to induce an immune response. The mRNA is taken in by our cells, and the viral protein or signaling molecule that is normally found on the outside of the virus-cell, is produced, causing our immune system to recognize and create antibodies against that pathogen. Antibodies are proteins that our immune system creates in order to identify pathogens, and notify different immune cells to fight invaders. Antigens are any foreign material that antibodies can detect. There is no virus, dead or alive, inside these vaccines.
Even before the United States had its first COVID-19 cases, the mRNA vaccines were in development. The technology underpinning the vaccine’s development had been discovered in 2005, and plans were already in place to develop vaccines using this technology.
“We were working on … Coronaviruses with Moderna since 2017… with the plan that we would design the antigens and they would deliver it with mRNA and that would be our plan for pandemic preparedness,” said McLellan.“This was a confluence of events that you couldn’t have imagined … it all came together with all the right information and all the right tools from a number of threads…”
These vaccines have saved millions of lives over the course of the pandemic and the technology is set to save many more, in diseases other than COVID-19.
“We have vaccines for HIV, Hepatitis C, Malaria, Genital Herpes, Norovirus and a bunch of others that are going into clinical trials…” Weissman said. “I’m very interested in sickle cell treatments because it has enormous potential to treat a really horrible disease that’s very poorly treated nowadays…. Once we develop that, we can use it to cure many other diseases, so its the beginning of a new platform technology”
Even as progress is made in developing new vaccines, the world still faces issues with vaccine distribution and treatment. COVID-19 is not yet over as cases rise in China and South Africa, with the new Omicron subvariant BA.4 arising.
“Most manufacturers have largely spurned the opportunities to share technology and know-how and public health-oriented licensing, despite a number of mechanisms being set up…” the World Health Organization said. These mechanisms include COVAX, a global vaccine sharing agreement, but wealthy countries globally continue to hoard vaccines.
[The U.S. government’s] primary concern is treating Americans and using American tax money to treat Americans. I don’t think people understand how important it is to vaccinate the entire world because variants are going to keep appearing as a function of how many people are getting infected,” Weissman said, “So it’s great to vaccinate your population but until you vaccinate the world variants are going to keep coming…”
Natalie Ringdahl is a STEM Intern for the spring 2022 quarter. She can be reached at email@example.com.
Sierra Howard is a STEM contributing writer. She can be reached at firstname.lastname@example.org.