AAVCOVID Releases Preclinical Data on Single-Dose, Room Temperature-Stable COVID-19 Vaccine Supported by New Funding

Up to $2.1 million award from the Bill & Melinda Gates Foundation to enable Mass General Brigham and Penn Medicine’s AAVCOVID platform, with single-dose vaccines that can be stored at room temperature for up to one month and showed efficacy and safety in animal models, to enter phase I clinical trials overseas.

Boston, Mass. — The AAVCOVID vaccine program, a novel gene-based vaccine strategy that utilizes an adeno-associated virus (AAV) vector, was granted an award for up to  $2.1 million from the Bill & Melinda Gates Foundation. In data released in preprint, two AAVCOVID vaccine candidates led to robust neutralizing antibody responses in mouse and nonhuman primate models from only a single dose. The candidates were also shown to be safe and well-tolerated in both models. The AAVCOVID vaccine program was founded at Mass General Brigham at the outset of the pandemic.

Testing the vaccines’ stability and potency at different temperatures revealed that AAVCOVID candidates remained potent and effective when stored at room temperature for up to one month. This room temperature stability and the fact AAVCOVID vaccines do not require cold-chain freezer storage, could enable this AAV-based platform to develop a vaccine for COVID-19 and other diseases for developing countries without the necessary cooling infrastructure some vaccines require. These results were published online recently as a preprint in bioRxiv and are being submitted to a peer-reviewed journal.

The grant from the Bill & Melinda Gates Foundation  will aid the effort to bring further preclinical validation to the AAV vaccine platform. An AAVCOVID vaccine candidate is set to enter clinical trials in 2021.

“We are extremely grateful and humbled to be one of the COVID-19 vaccine efforts to be awarded financial support by the Bill & Melinda Gates Foundation,” said AAVCOVID principal investigator 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. “We share a desire to develop vaccines that can end the threat of this deadly disease globally. We believe our data on single dose immunogenicity and room-temperature stability holds promise to overcome key logistical challenges to an effective vaccine campaign in this global crisis, particularly in countries with limited infrastructure.”

AAVCOVID is developed through an academia-industry consortium with groups within Mass Eye and Ear, and Massachusetts General Hospital, both member hospitals of Mass General Brigham in Boston, the University of Pennsylvania in Philadelphia and Novartis Gene Therapies. Dr. Vandenberghe is working in conjunction with program co-leaders Mason Freeman, MD, who serves as director of the Translational Medicine Group of the Mass General Center for Computational and Integrative Biology and is Professor of Medicine at Harvard Medical School, and gene therapy pioneer James M. Wilson, MD, PhD, director of the internationally-renowned Gene Therapy Program at the University of Pennsylvania. Novartis Gene Therapies contributes to the consortium its unique technology, expertise and supply chain to manufacture at-scale AAVCOVID for clinical trial testing through an in-kind partnership.

The rapid development of AAVCOVID was initially made possible through research support from Mass Eye and Ear with additional support from the Department of Ophthalmology, led by Joan W. Miller, MD, Chief of Ophthalmology at Mass Eye and Ear, Massachusetts General Hospital, and Ophthalmologist-in Chief at Brigham and Women’s Hospital, and Chair of Ophthalmology and David Glendenning Cogan Professor of Ophthalmology at Harvard Medical School. The initial work was also funded by Individual donations including a lead gift from Celtics co-owner and former Mass Eye and Ear Board Chairman Wyc Grousbeck and Emilia Fazzalari, research grants from the Harvard-led Massachusetts Consortium for Pathogen Readiness and FastGrant, and manufacturing partnerships with Aldevron, Catalent and Viralgen.

Animal efficacy data shows robust immune response and safety

Researchers tested two vaccine candidates of AAVCOVID that were qualitatively different in how they would elicit an immune response. They tested each candidate in mouse and nonhuman primate models at different doses to determine safety and immunogenicity (the ability to produce an immune response).

The immunogenicity following a single intramuscular injection was shown to be potent in inducing neutralizing antibodies in two mouse strains and both genders, a mouse model for aging and an obese mouse model. Both vaccine candidates demonstrated durable responses from a single dose administration for at least three months. Early onset of antibody responses were seen by day 14 and rates increased over time.

In non-human primates, AAVCOVID candidates were shown to retain peak immunogenicity for at least five months following a single-dose injection. Responses in both animal models were complemented by functional memory T-cell responses, important to confer durable immunity.

Mice and nonhuman primates tolerated the vaccine candidates well with no adverse safety events observed. While these results need to be confirmed in human studies in healthy volunteers, the researchers hope the favorable safety profile of established AAV-based gene therapies already approved for use in Europe and the U.S. -- which are often given at much higher doses in patients -- will translate to the vaccine. 

Experimental vaccine designed to address dosing and cold-chain challenges

The researchers also sought to address two logistical and biological hurdles to global distribution: the need for simplicity of the dosing regimen and limited dependency on cold-chain infrastructure, or the need for freezers for storage and transport.

Many COVID-19 vaccines require two doses, which may raise adherence concerns since people require two separate appointments weeks apart. Doubling the dose needed also increases costs, need for logistical support and manufacturing needs. Following testing, AAVCOVID, was shown in both mouse and nonhuman primate models to lead to robust neutralizing antibody responses from only a single dose.

Another hurdle for some leading vaccines is they require below-freezing temperatures for storage that require special freezers that are not widely available. AAVCOVID candidates were stored at different temperatures and the researchers found they maintained stability and potency at up to room temperature for one month. This room temperature stability is in line with other AAV-based medications already in use. Without the need for freezing temperatures, Dr. Vandenberghe hopes such a vaccine if validated in human studies can be distributed in regions of the world with poor health care infrastructure that lack adequate refrigeration capabilities.

Program seeks to leverage existing manufacturing capacity

The AAVCOVID vaccine program is a gene-based vaccine strategy that seeks to deliver genetic sequences of the SARS-CoV-2 using an AAV vector. Vaccination delivers genetic DNA fragments of SARS-CoV-2 which generate a coronavirus spike antigen protein that is designed to elicit an immune response to prevent infection.

Dr. Vandenberghe and his laboratory began work on the vaccine in mid-January 2020 following the Wuhan outbreak and the first publication of genetic sequences of the new coronavirus. AAVCOVID uses a specific AAV called rh32.33 with desirable inflammatory properties needed for vaccines and lacks pre-existing immunity in humans.

AAVCOVID seeks to induce immunity to prevent infection and or disease in healthy populations, leveraging the existing manufacturing capabilities of an established AAV gene therapy industry. The program has a manufacturing agreement with several gene therapy industry partners led by Novartis Gene Therapies, to help reach the scalability goals in the event of approval. The company is one of the first in the world to have successfully scaled up gene therapy manufacturing with over 1 million square feet of manufacturing capacity.

About Mass Eye and Ear

Massachusetts Eye and Ear, founded in 1824, is an international center for treatment and research and a teaching hospital of Harvard Medical School. A member of Mass General Brigham, Mass Eye and Ear specializes in ophthalmology (eye care) and otolaryngology–head and neck surgery (ear, nose and throat care). Mass Eye and Ear clinicians provide care ranging from the routine to the very complex. Also home to the world's largest community of hearing and vision researchers, Mass Eye and Ear scientists are driven by a mission to discover the basic biology underlying conditions affecting the eyes, ears, nose, throat, head and neck and to develop new treatments and cures. In the 2020–2021 “Best Hospitals Survey,” U.S. News & World Report ranked Mass Eye and Ear #4 in the nation for eye care and #6 for ear, nose and throat care. For more information about life-changing care and research at Mass Eye and Ear, visit our blog, Focus, and follow us on Instagram, Twitter and Facebook.