COVID-19 Resource Center

COVID-19 Resource Center

Source: Healio Interviews
Disclosures: Miller reports no relevant financial disclosures.
June 03, 2020
4 min read

Experimental gene-based COVID-19 vaccine holds promise for fast development

Source: Healio Interviews
Disclosures: Miller reports no relevant financial disclosures.
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An experimental gene-based vaccine candidate against SARS-CoV-2 is currently under development at Massachusetts Eye and Ear and Massachusetts General Hospital.

Leading this vaccine program is Luk H. Vandenberghe, PhD, director of the Grousbeck Gene Therapy Center at Massachusetts Eye and Ear and associate professor of ophthalmology at Harvard Medical School.

C3 Photo
The AAV capsid is used as a trojan horse to deliver a genetic component of the coronavirus to raise an immune response. Source: Eric Zinn and Luk H. Vandenberghe, PhD

“There is an extraordinary connection with ophthalmology, which may not be so surprising if you think that Luxturna (voretigene neparvovec-rzyl, Novartis), a breakthrough treatment for retinitis pigmentosa, was the first approved gene therapy in the U.S. Dr. Vandenberghe began to work on gene transfer technology 20 years ago as a molecular bioengineer, initially at Penn Medicine with Jim Wilson and Jean Bennett, and was attracted to ophthalmology because ophthalmology was leading in gene therapy,” Joan W. Miller, MD, chief of ophthalmology at Massachusetts Eye and Ear and chair of ophthalmology at Harvard Medical School, said in an interview with Healio/OSN.

Joan W. Miller, MD

While at Penn, Vandenberghe developed a novel adeno-associated virus (AAV) vector that caused a strong immune response. This specific characteristic made it unsuitable for gene therapy but was ideal, potentially, for a vaccine. He called it “my blue whale,” and with this in mind, he kept it on hold. In 2012, he joined the leadership of the Ocular Genomics Institute at Massachusetts Eye and Ear and Harvard Medical School and worked with the group of Eric Pierce, MD, PhD, and Jason Comander, MD, PhD, at bench-to-bedside programs on gene therapy for blinding disorders.

“In mid-January this year, when the Wuhan virus sequence was published, Luk started working on a possible vaccine. What was initially just a side project quickly developed into what we hope will be a successful program,” Miller said.

The AAVCOVID vaccine program is a unique gene-based vaccine strategy that uses Vandenberghe’s “blue whale,” an AAV vector, to deliver genetic sequences of the SARS-CoV-2 spike antigen.

“The advantage of this technology is that it uses a harmless viral vector with an established safety record, already approved by the FDA and other regulatory bodies to treat retinitis pigmentosa (Luxturna) and spinal muscular atrophy (Zolgensma, AveXis). There is substantial, well-established experience and capacity worldwide for manufacturing AAV-based drugs, and this will help to quickly scale up the development of and access to the vaccine,” Miller said.

The early data are promising, and there is hope that a single intramuscular injection will induce a potent immunity to SARS-CoV-2, with no need for boosters. After preclinical findings, two vaccine candidates will advance into the clinical phase of testing in humans.


“We expect to do the first clinical trial at Massachusetts General Hospital, with another important leader of this program, Dr. Mason Freeman. The normal time frame for the development of a vaccine is several years, but in all countries there has been an acceleration, and we hope to be able to start the clinical trial in the second half of 2020. We don’t need huge numbers, and if everything is favorable, we could have something already by the end of the calendar year. That might be optimistic, but all the programs are on a rapid timeline,” Miller said.

Funding is another critical point. A lot of the early funding has been through philanthropic support led by Wyc Grousbeck, lead owner and CEO of the Boston Celtics and past chairman of Massachusetts Eye and Ear, and his wife, Emilia Fazzalari. Vandenberghe also received grants and support from several organizations and industry partners, but more is needed to develop the entire project.

Various partnerships have been established to help the AAVCOVID vaccine program reach its goal of creating a vaccine with potential for scalability. The Gene Therapy Program at the University of Pennsylvania has joined the AAVCOVID vaccine program as an equal partner, which will enable additional rounds of preclinical studies that are needed for the FDA’s investigational new drug application process, according to a press release from Massachusetts Eye and Ear.

AveXis, a Novartis company, has begun manufacturing the vaccine and is contributing its technology, expertise and supply chain at no cost to supply the AAV vaccine for COVID clinical trials, the release said. As well, industry partnerships have been expanded to include manufacturing agreements with Viralgen, Aldevron and Catalent, whose “partnership with AAVCOVID provides immediate support toward clinical trial readiness, production of vaccine dose under Good Manufacturing Practice conditions and scalable processes to address future supply,” the release said.

The AAVCOVID vaccine program is a bright example of the positive response to the pandemic that has come from many parts of the world.

“In the midst of the COVID-19 emergency, while keeping up with the hard work of coping with COVID-19 at the hospital, it is a light in the course of the day to be involved in this project,” Miller said.

There are many vaccine programs currently going on around the world, and multiple successes are needed to provide enough vaccines for the entire global population. The AAVCOVID program could be scaled up rapidly because there are existing manufacturers all around the world that will be able to switch from making AAV gene therapies to making a vaccine.


“That would go a long way for making it available for people, probably faster than other vaccines, though we must hope that multiple programs will be a success,” Miller said.

Another advantage is that AAV is an adaptable technology. If the SARS-CoV-2 virus mutates, it will take just a few weeks to exchange the genetic code inside the AAVCOVID vaccine for an updated genetic code and process it into an updated vaccine.

For more information: Joan W. Miller, MD, can be reached at Massachusetts Eye and Ear, 243 Charles St., Boston, MA 02114; email: