Labs Are Experimenting With New—But Unproven—Methods to Create a Coronavirus Vaccine Fast

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Gene-Based Vaccines

Theoretically, the simplest and fastest way to make a vaccine would be to have a person’s own cells produce minute quantities of the viral protein that trigger an immune response. To do that researchers are turning to genetics.

The first genetic approach uses DNA. A single gene that codes for a protein from the coronavirus is injected into the patient’s cells in the hopes that a small fraction of the DNA molecules will find their way into the cell nucleus. There they would be copied into an RNA molecule which is then read by the cell to produce the viral protein. But it is difficult to get the human body to produce enough protein using this approach. Frequently, very little DNA makes it to the cell nucleus and the cell does not produce the protein in sufficient quantity to trigger a strong enough immune response.

As of yet, there are no DNA vaccines currently approved by the FDA for human use and the success of this method has been limited. But there is promise. In 2016, several groups developed candidate Zika vaccines using this technology and at least one company, INOVIO Pharmaceuticals, Inc. is developing INO-4800, a DNA vaccine candidate for the coronavirus.

The bottleneck of DNA vaccines is getting the DNA to the nucleus to be transcribed into RNA. Vaccines that use RNA directly might be able to overcome this problem. Since RNA is translated into proteins as soon as it enters the cell, this approach results in stronger immune responses than DNA vaccines. However, RNA breaks down faster than DNA.

This has not deterred a number of companies from trying it though. Notable in the U.S. is Moderna, and on March 16, the National Institutes of Health started a clinical trial of Moderna’s lead coronavirus vaccine candidate, mRNA-1273.

Manufacturing DNA and RNA relies on standardized and fairly simple processes. DNA vaccines are produced in bacteria that grow overnight while RNA vaccines are produced in test tubes using a biochemical reaction that only takes hours. Gene-based vaccines could be produced extremely quickly compared to traditional or protein-based vaccines.

Friendly Virus Vaccines

The main issue with gene-based vaccines is getting the DNA or RNA to where it needs to be. One elegant way to solve this challenge is to use a harmless virus as a delivery system. Viruses are extremely good at penetrating cells; once inside, a virus with genes from SARS-CoV-2 could use the machinery of the cell to produce proteins to trigger an immune response for the coronavirus.

This technique is being pursued by a few companies around the world. For example, Hong Kong-based CanSino Biologics is inserting the coronavirus gene that codes for the spike protein into an adenovirus. They used this strategy to produce the first government-approved Ebola vaccine, and clinical trials of an engineered adenovirus that would protect against the coronavirus have already started in China.

The production of vaccines delivered by harmless viruses is slower than producing DNA or RNA vaccines because it involves the culture of slow-growing mammal cells. However, like the production of gene-based vaccines, they rely on existing processes that take advantage of viruses that have been optimized for manufacturing.

Containing the Epidemic with Imperfect Vaccines

While the pace of COVID-19 vaccine development is unprecedented, the timeline to mass vaccination still remains uncertain. While the large number of approaches being pursued may give the impression of desperation and confusion, it is actually reassuring. This multipronged approach is a way to hedge the vaccine development bet.

It is unlikely the first vaccines developed will be 100 percent effective and easy to produce on a massive scale. Realistically, researchers will develop a number of good-enough vaccines that can be produced using different kinds of manufacturing infrastructures. While these vaccines may at first have a limited efficacy, the diversity in manufacturing processes will allow companies to make and distribute them quickly, buying time and helping contain the current epidemic and prevent future outbreaks.

This article from Jean Peccoudprofessor and Abell Chair in Synthetic Biology at Colorado State University, was originally published at The Conversation.

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