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How coronavirus vaccine candidates vary in approach

Explaining the five leading strategies
Research on remdesivir enters new phase
Posted at 6:02 PM, Aug 05, 2020

SAN DIEGO (KGTV) — In the race for a coronavirus vaccine, scientists often say we need more than one winner.

That’s in part because different vaccines use different strategies to provoke the immune system, and each strategy has different strengths.

Take the inactivated virus vaccine, an approach currently used in the vaccine against the poliovirus. In this approach, scientists take a live virus, kill it with chemicals or heat, and then introduce that viral corpse into a person.

There are three groups in the final phase of human trials using inactivated coronavirus, primarily in China, according to a tracker from the Milken Institute.

“The immune system can tell the difference between something that's a real threat and something that's not a threat, and so if you get injected with a dead virus your immune system has the tendency to not pay a lot of attention to that,” said Dr. Shane Crotty of the La Jolla Institute for Immunology.

The downside of the inactivated virus approach is that it only elicits two out of the three of the parts of the immune system, Dr. Crotty said. It’s capable of producing antibodies and helper T-cells, but not killer T-cells.

The modern take on the inactivated virus approach is called a viral vector vaccine.

In this strategy, scientists combine elements of the coronavirus with a common cold virus called an adenovirus that won’t make you sick. Since the virus is alive, it can elicit all three kinds of immune responses, Dr. Crotty said.

“There are no licensed vaccines right now that use that strategy, but there are all kinds of vaccine trials that have been done around the world with those types [of vaccines] showing that they're straightforward to manufacture. They're very safe,” he said.

The University of Oxford is testing a viral vector vaccine for COVID-19 in a Phase 3 clinical trial.

Then there are subunit vaccines. These include just a section -- or subunit -- of the virus’ protein.

UC San Diego is working on a coronavirus candidate vaccine using this approach.

There are subunit vaccines currently on the market for tetanus and other viruses.

“Working with proteins is more challenging, just from a laboratory and manufacturing perspective,” Dr. Crotty said.

Enter the next phase of vaccine development. Instead of using the virus itself or fragments of it, Inovio Pharmaceuticals is working on a vaccine strategy using just the virus’ genetic information.

DNA-based vaccines simply introduce a genetically engineered blueprint of the virus into a person, and the cells do the rest.

“Some people get confused about this. They think it’s a genetic vaccine that changes their DNA and becomes part of them, and that’s definitely not the case.” Dr. Crotty said. “They don’t become part of you. Your body chews them up.”

Researchers have been working on DNA-based vaccines for about 20 years, Crotty said, but none are currently licensed for use.

San Diego-based Arcturus Therapeutics is using an RNA-based approach, along with other companies like Pfizer and Moderna that have entered Phase 3 trials.

Messenger RNA reads the DNA instructions and helps translate them into proteins.

Dr. Crotty said the DNA and RNA approaches have similar drawbacks and benefits: they’ve never been approved for us, but both can be developed rapidly because they don’t require access to the physical virus.

Around the world, there are more than 200 coronavirus vaccines currently in development, according to the Milken Institute.