Big gene therapy names line up behind experimental Covid-19 vaccine

An early stage vaccine against Covid-19 based on the same basic technology used in gene therapy is gaining some support from some of that field’s biggest names.

Earlier this year, James Wilson, a gene therapy pioneer, got a call from Luk Vandenberghe, who had been a graduate student in Wilson’s lab two decades ago. Vandenberghe wondered if a virus they had worked on as a potential component of gene therapies might work as part of a vaccine against SARS-CoV-2, the coronavirus that causes Covid-19.

“It’s a great idea,” said Wilson, who heads the Gene Therapy Program at the University of Pennsylvania. “What can I do to help?”

Vandenberghe, director of the Grousbeck Gene Therapy Center at Massachusetts Eye and Ear, is taking Wilson up on his offer. On Thursday, the Grousbeck center announced a collaboration with Penn to conduct necessary animal tests of the new gene therapy, called AAVCOVID. At the same time, AveXis, the gene therapy unit of the drug giant Novartis, has signed up to manufacture supplies of the experimental vaccine for human clinical trials at no cost. The studies are expected to begin in the second half of this year.

There is a desperate need for speed, and to develop every potential vaccine candidate, Vandenberghe said, because it is uncertain what will work.

“Every dose of a somewhat efficacious vaccine will be consumed,” Vandenberghe said. “This is not ‘first to market.’ This is all hands on deck.”

David Lennon, the president of the AveXis unit, said that Novartis did not want the process of hammering out a deal to slow down Vandenberghe clinical studies.

“At this point, given the early nature of the technology, as well as the speed at which we wanted to move and the fact that this is a public health emergency, we didn’t want to spend time worrying about exactly where the commercial aspects of this partnership land,” Lennon said.

Three contract manufacturing players, Viralgen, Aldevron, and Catalent, have also signed on to help with manufacturing.

The reason all these companies — and Wilson — can sign on to make this vaccine is that it uses the same type of virus, known as an adeno-associated virus, that is the backbone of most gene therapies. Gene therapy tries to replace missing or damaged genes by using a virus to sneak the genetic material into cells, which is, basically, what viruses do. Some vaccine technologies, including those being developed for Covid-19, try to take a similar approach.

One big difference: the amount of AAV in a vaccine would be 1,000 to 10,000 times smaller than in gene therapies such as Novartis’ Zolgensma, which treats a rare and lethal disease called spinal muscular atrophy in infants.

Gene therapy researchers turned to adeno-associated virus in the 2000s after a disaster. A patient in a study run by Wilson employing a gene therapy that used adenovirus, which causes flu-like symptoms, had an immune response that led to organ failure and death. As a result, the entire field, which had seen on the cusp of developing treatments, was effectively frozen. 

Unlike adenovirus, adeno-associated virus, or AAV, is very good at evading the immune system, which means that it doesn’t provoke that kind of response. But the virus Vandenberghe developed while working with Wilson, which was derived from AAVs found in monkeys, did provoke the immune system somewhat.

While that meant this particular type of AAV was not suited to gene therapy, provoking the immune system is exactly what researchers want a vaccine to do. In fact, several other Covid-19 vaccines use an adenovirus to deliver a genetic payload that then provokes an immune response.

The adenovirus was a necessity for developing, for instance, experimental HIV vaccines, Vandenberghe said. But he thinks AAV may have advantages when it comes to Covid-19, including safety. Another advantage is easy to understand: all the manufacturing capacity for growing AAV that companies like Novartis have built in order to be able to manufacture gene therapy products.

“Yes, we are six months or so delayed compared to some of the first movers,” Vandenberghe said, “but in the end we will need something that is highly safe, highly potent, and highly scalable. And we believe we check boxes in each of these three categories.”

Now he has to conduct the studies to find out whether or not he is right.

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