Gene Vaccine

HMS researchers advancing experimental gene-based COVID-19 vaccine


This article is part of Harvard Medical School’s continuing coverage of medicine, biomedical research, medical education and policy related to the SARS-CoV-2 pandemic and the disease COVID-19.

Harvard Medical School researchers based at Massachusetts Eye and Ear and Massachusetts General Hospital are announcing progress towards the testing and development of an experimental vaccine called AAVCOVID—a novel gene-based vaccine candidate against SARS-CoV-2, the virus that causes COVID-19.

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The AAVCOVID vaccine program is a gene-based vaccine strategy based on an adeno-associated virus (AAV) vector, a harmless viral carrier that serves as a delivery vehicle into the body.

Vaccination with AAVCOVID delivers genetic sequences of the SARS-CoV-2 spike protein—the characteristic protuberances on the coronavirus that it uses to enter host cells—so the body can develop an immune response to the virus.

AAV technology has been used extensively in the field of gene therapy, and substantial experience and capacity exists for manufacturing and clinical use of AAV-based medicines. Two AAV-based drugs have been approved by U.S. Food and Drug Administration in recent years.

“AAV is a superior technology for safe and efficient gene delivery, and the unique technologies we are applying in AAVCOVID support the potential for a potent immunity to be induced to SARS-CoV-2 from a single injection,” said Luk Vandenberghe, HMS associate professor of ophthalmology at Mass. Eye and Ear, whose laboratory developed the AAVCOVID vaccine program.

“In a crisis, we can harness the power of molecular biology and develop a draft of a vaccine in weeks, and that’s what was done here. Now, clinical studies are needed to establish safety and efficacy of our novel approach,” said Vandenberghe, who is director of the Grousbeck Gene Therapy Center at Mass Eye and Ear.

Vandenberghe and his laboratory began work on the vaccine in mid-January following the Wuhan outbreak and the first publication of genetic sequences of the new coronavirus.

While several types of COVID-19 vaccines are in development worldwide, AAV technology offers several distinct advantages, including its adaptability and potential to elicit a beneficial immune response in people. In addition, other versions of AAV technology have been tested in the clinic for more than two decades with a favorable safety record.

Unique approach

The vaccine program is currently in preclinical development with a plan to begin clinical testing in humans later this year. Mason Freeman, HMS professor of medicine and director of the Translational Research Center at Mass General, is leading the efforts to develop the clinical studies intended to establish safety and efficacy of the experimental vaccine.

”While many organizations are engaged in generating vaccine candidates to prevent COVID-19 disease, it is very far from certain what the best approach will be,” said Freeman. “This unique vaccine method brings an elegant, novel and extremely creative approach to meeting our goal: to protect our most vulnerable patients as well as the health care workers who care for them during this and future viral outbreaks.”

AAV is also a rapidly adaptable technology. If a new strain of the SARS-CoV-2 virus emerges, the genetic code inside the AAVCOVID vaccine can be exchanged for an updated genetic code and processed into an updated vaccine in weeks, according to the researchers.

The AAVCOVID vaccine candidate will be administered by an intramuscular injection. Currently, tests are underway in animal models, and initial manufacturing activities have begun. Based on the preclinical findings, one or more candidates will advance into the clinical phase of testing in humans.

The team is advised by experts at Mass General and the Mass General Brigham Innovation Fund and includes involvement of experts from industry with experience in vaccine development, regulatory affairs and manufacturing.

“This is what innovation looks like. It is a combination of both the scientific insight of Dr. Vandenberghe and his team as well as the nimble and collaborative spirit of the institutions and donors who have come together to move this program from idea to promising vaccine candidate at lightning speed,” said Joan Miller, the David Glendenning Cogan Professor of Ophthalmology at HMS and chief of ophthalmology at Mass. Eye and Ear.

“We are deeply grateful to all involved in this collaboration, and especially to the donors who generously stepped up to spearhead the initial funding of this program,” said John Fernandez, president of Mass. Eye and Ear.

“The unprecedented coronavirus pandemic has challenged us all, and overcoming it demands the best thinking and the most creative ideas from our scientific and clinical teams supported and strengthened by our philanthropic communities,” said Peter Slavin, president of Mass General and professor of health care policy in the Blavatnik Institute at HMS. “This collective spirit of innovation, resolve and generosity is the most powerful weapon we have to fight this formidable virus.”

The research is funded by philanthropic support led by Wyc Grousbeck, Emilia Fazzalari and others.

Adapted from a Mass Eye and Ear news release.
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