Gene Therapy for Blindness May Hold Key to Coronavirus Vaccine

Written By: Reena Mukamal and published by the American Academy of Ophthalmology on May 14, 2020.

A COVID-19 vaccine unlike any other in development is gaining attention.

The experimental vaccine, called AAVCOVID, could end the coronavirus pandemic in record time, experts say. That’s because it relies on a gene therapy technology that’s already in use to cure a form of blindness.

Two Harvard-affiliated hospitals are spearheading the research, and the vaccine is expected to be tested in humans before the end of this year.

Is there a vaccine for the coronavirus?

Not yet. There are more than 100 different COVID-19 vaccines in development around the world. Some are already in clinical trials.

But AAVCOVID has a unique advantage: It relies on gene-transfer technology that’s already approved by the FDA to treat inherited blindness (Luxturna) and spinal muscular dystrophy (Zolgensma).

At the center of this technology is a harmless virus, called adeno-associated virus (AAV), that has been tested for more than two decades and is proven safe for humans.

“AAV is a harmless viral vector with an established safety track record. It already has a manufacturing industry because of its ongoing use in gene therapy,” says Joan W. Miller, MD, chief of ophthalmology at Massachusetts Eye and Ear, Massachusetts General Hospital, and Brigham and Women’s Hospital, and chair of ophthalmology and the David Glendenning Cogan Professor of Ophthalmology at Harvard Medical School.

Because multiple drug companies already make AAV, vaccine production could be scaled up quickly to meet global demand.

How does the experimental COVID-19 vaccine work?

The new vaccine packages a fragment of genetic code from the coronavirus (SARS-CoV-2) into the harmless virus (AAV), which would normally deliver a gene therapy.

But this time, instead of delivering a gene therapy, the AAV will deliver instructions for making the so-called ‘spike’ protein that sits on the surface of the coronavirus.

Exposing the body to the spike protein alone, without the rest of the deadly coronavirus, should teach the immune system to recognize and fight off future infections of COVID-19. Unlike the AAVs used in gene therapy, the one used in AAVCOVID excites the immune system — an essential feature of a successful vaccine.

“The particular AAV we are using elicits a strong immune response in experiments. This may allow for a single vaccination instead of the two injections required with many vaccines,” Miller says.

Even if the coronavirus mutates and a new strain emerges, the genetic instructions can be switched out — and an updated vaccine made — in just a few weeks.

The vaccine has captured the support of heavy hitters such as Wyc Grousbeck, owner of the Boston Celtics, who has donated $1 million to the AAVCOVID research project.

Ophthalmologists helped develop the coronavirus vaccine candidate

The experimental AAVCOVID vaccine — spearheaded by Luk H. Vandenberghe, PhD, director of the Grousbeck Gene Therapy Center at Massachusetts Eye and Ear — has roots in ophthalmic research.

The technology platform can be traced back to physician and molecular geneticist Jean Bennett, MD, PhD, and her husband, ophthalmologist Albert Maguire, MD. Their AAV work led to the FDA approval of the first gene therapy cure for blindness, Luxturna, in 2017.

“This first approval set standards and pathways for the field that now allow for other AAV approaches, such as AAVCOVID, to move much faster through the regulatory pipeline due to the precedent,” says Miller.

That said, the novel coronavirus is not yet well understood. An AAV-based vaccine has never been used in humans, and AAVCOVID must undergo further safety studies before entering human trials. 

If those studies go well and regulatory approval is granted, the team intends to begin testing the vaccine in human clinical trials this summer. Those clinical studies will be led by Mason Freeman, MD, director and founder of the MGH Translational Research Center and a professor of medicine at Harvard Medical School.