Yale researchers pursuing COVID-19 vaccine based on powerful Yale platform

The urgent search for a vaccine to protect against COVID-19 is well underway, with a number of experimental gene-based vaccines in various stages of development by biotech companies and academic scientists worldwide. Yale pathologist John “Jack” Rose believes a proven vaccine platform he pioneered decades ago using a livestock virus called vesicular stomatitis virus (VSV) could produce better immunity than other candidates, and be scaled up quickly to meet global demand.

The VSV platform was used to develop the Ebola vaccine that received FDA approval in December 2019 and has since been effectively administered to more than 235,000 people, including over 60,000 health care and frontline workers.

Rose, professor emeritus of pathology and senior research scientist at Yale, and a small team of researchers that includes pathology chair Dr. Chen Liu and Craig Wilen, assistant professor of laboratory medicine and of immunobiology, are now working around the clock to develop a VSV-based COVID-19 vaccine and begin animal testing.

“It is so critical that we provide at least an alternative approach for a vaccine,” said Liu, who enlisted Rose in the challenge and set up his own lab alongside Rose’s to share in the work. “There are DNA or protein-based vaccines for COVID-19 in trials, but, in my opinion, the viral vector [a vaccine using a live virus] would be more robust in generating immunity.”

To make a vaccine using the VSV platform, scientists insert a protein from the virus they are trying to protect against — such as Ebola or SARS CoV-2, the virus strain that causes COVID-19 — into the livestock virus. The livestock virus is well suited for safely passing genetic material into cells and stimulating an immune response, Rose said. It is genetically stable, does not cause illness in humans, and generates a very strong antibody and T-cell response.

And a livestock virus can be reproduced much more easily than messenger RNA and DNA vaccines.

“It would be easy to scale up production of a VSV vaccine for SARS CoV-2,” said Rose. “We could get to millions of vaccine doses easily.”  

Wilen’s lab is growing the live SARS CoV-2 virus strain, necessary for testing the new vaccine’s effectiveness.

He’s also making synthetic versions of the virus’ spike protein that will be inserted into the livestock virus. In high-resolution electron micrographs of the SARS CoV-2 virus, the spike proteins appear as protrusions emerging from the central mass like so many sucker feet. It’s these proteins that allow the virus to bind to human cells and cause infection.

Because SARS CoV-2 is so contagious and potentially lethal, the Yale scientists wear complete protective gear — including respirators — and work in an isolated, negative-pressure room.

“The coronavirus is similar in terms of virology to the norovirus,” Wilen’s focus before the pandemic hit, he said. “We were the first lab at Yale to culture the virus. We’re working to pop out the normal VSV protein called ‘G’ and swap it with the coronavirus protein.”

Wilen said he and two postdoctoral students have taken over additional lab space in order to practice social distancing while they work.

The scientists have reason to hope that their VSV-based COVID-19 vaccine will work. Beyond its successful use in protecting against Ebola, the VSV platform has been used to develop other vaccine candidates that have shown promise in animal models for protecting against avian flu, HIV, and SARS CoV-1. The latter virus spread across 26 countries in 2013 and led to over 8,000 cases and 774 deaths.

“SARS CoV-2 is a stealth version of SARS,” Rose said. “The original SARS made people very sick much faster and it was easier to trace contacts.”

In his work creating the original SARS vaccine, Rose was able to successfully insert the spike protein into the VSV virus and engineer protection against SARS in mice. Because that virus was easier to contain than the slow-to-emerge SARS CoV-2, the work ended before the vaccine reached human trials.

But he learned important lessons about how the novel coronavirus operates. For one, it’s hard to generate immunity against it.

“Even with the live virus, SARS CoV-1 didn’t get a strong immune response [in mice],” Rose said. “It was protective, but low. It suggests we need a robust vector system.”

Preliminary data shows that inserting SARS CoV-2 into the VSV platform will work to generate that protective immune response, Rose said.

Said Liu: “This has a really good chance.”