From ‘Whole Virus’ to ‘Replicating RNA’ Vaccines, a Scientist Explains the Basics

► Video with Interactive Transcript

Scientists working furiously on more than 165 different coronavirus vaccines are likely to develop a range of solutions, each of which could be effective for different patients and in different situations, according to a University of Washington microbiologist.

“I don’t believe there’s going to be one single silver bullet,” said Deborah Fuller, who has spent her career developing vaccines against HIV and other infectious diseases, including coronavirus. “I don’t think one vaccine is going to be able to do it all. … It’s going to be a combination of multiple vaccines to be able to cover the different demographics, to be able to distribute it worldwide and to induce the best immunity.”

In a session (transcript) with National Press Foundation fellows, Fuller gave a quick vaccines 101 tutorial – active and passive immunization, herd immunity, how a vaccine introduces an antibody response. She explained why her lab believes a “self-amplifying replicating RNA vaccine” could be a promising approach.

The goal for vaccine developers is to induce a “memory” that causes a body’s immune system to remember a viral invader it has seen before. There are several different methods for doing so. Common vaccines for measles and mumps, for example, incorporate an inactivated or weakened form of the virus that doesn’t cause the disease but does cause the immune system to make antibodies to fight it. The immune system remembers what it has seen before and fights off the virus the next time it comes knocking.

The ideal vaccine would produce a quick immune response, ideally with just one dose; create antibody and T-cell responses; work across different age groups and demographics; be manufactured quickly; and be stored at room temperature.

Fuller said researchers are trying nine different approaches to develop a coronavirus vaccine. Traditional ones include “attenuated” vaccines, used against measles, and “inactivated” ones, used to create the annual flu shot. (For a good overview, see work in The New York Times and The Washington Post; for an interview with Fuller, see Crosscut.)

Fuller explained each of those, as well as the new approach she is exploring: an RNA vaccine.

The coronavirus – officially SARS-CoV-2 – is known for the distinctive spike proteins on its surface that allow it to infect human cells. Fuller’s approach is to inject a piece of genetic code called messenger RNA into cells to prompt the body to develop antibodies that attach themselves to the spikes. That immune response stops the virus.

Her lab is experimenting on a self-replicating messenger RNA vaccine that is delivered through a “lipid inorganic nanoparticle” – known as “LION.” It makes the vaccine more potent and stable at room temperatures.

RNA vaccines have never been approved for use, although they have been studied for years.

Fuller’s project has shown promising early results in animals. The replicating RNA vaccine produced antibodies against coronavirus in mice and primates with just one dose, and those effects occurred within two weeks. The LION approach is now in phase one human clinical trials.

Even so, the research community has been disappointed before, when such vaccines were first tested in the 1990s.

“What happened in the early stages of DNA and RNA vaccine discovery is that the first vaccines we tested looked great in animal models – great preclinical studies,” she said. “But the first DNA vaccines … were utter failures.”

While most researchers abandoned the field, Fuller and others held on, seeking to solve the problems that beset those early efforts. They had already progressed to human safety trials when the new coronavirus, SARS-CoV-2, hit. They were able to quickly pivot to developing a coronavirus vaccine using the same technology.

Even as the work on developing the testing that vaccine continues, manufacturers are producing and storing it in hopes of eventual approval and distribution.

“They’re doing this massive scale-up of the vaccine, storing it in the warehouse with a hope and expectation that the phase three trials will be successful.,” she said. “… They will either license it as successful, or they’ve got a whole warehouse of junk, and then it’s just a bust.”

Ultimately, five to seven different types of vaccines may be required to stop the pandemic, Fuller said.

This program is funded by GlaxoSmithKline LLC. NPF is solely responsible for the content.

Dr. Deborah Fuller
Professor, Department of Microbiology, University of Washington School of Medicine
Dr. Deborah Fuller on Vaccine Development 101
Subscribe on YouTube
More Presentations
Help Make Good Journalists Better
Donate to the National Press Foundation to help us keep journalists informed on the issues that matter most.
You might also like
Building a Vaccine Infrastructure
Ethics and the Coronavirus Vaccine
The Effects of Vaccine Hesitancy
The Ethics Behind Vaccine Trials
The Path to a Coronavirus Vaccine
The Race for a Coronavirus Vaccine
Vaccine Development 101
Tracking the Anti-Vaccination Movement
The Virus’ Long Timetable