New gene-based vaccine strategy receives grant from the Bill & Melinda Gates Foundation

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.

The grant 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.

The AAVCOVID vaccine program was founded at Mass General Brigham at the outset of the pandemic.

Preliminary tests of 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.

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. 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."

Luk H. Vandenberghe, PhD, AAVCOVID Principal Investigator and Director of Grousbeck Gene Therapy Center, Massachusetts Eye and Ear

Vandenberghe is anslo an Associate Professor of Ophthalmology at Harvard Medical School.

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.

Experimental vaccine designed to address dosing and cold-chain challenges

AAVCOVID aims 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. Testing thus far in both mouse and nonhuman primate models have shown a 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 have been 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.