Among the logistical challenges facing public health agencies that are struggling to vaccinate the masses against COVID-19 is that the two mRNA shots on the market, from Moderna and Pfizer, need to be stored at ultra-cold temperatures. Now, an alternative technology for shielding patients from the novel coronavirus—one that doesn’t pose that storage challenge—is showing early promise.
Two vaccine candidates built from gene-therapy technology and developed by Mass General Brigham scientists elicited strong immune responses in mouse and nonhuman primate models, the researchers reported on the journal preprint site bioRxiv. The team received a grant of up to $2.1 million from the Bill & Melinda Gates Foundation to further develop the vaccine technology, called AAVCOVID.
The vaccines, which remain stable when stored at room temperature, use an adeno-associated virus (AAV) vector to deliver genetic sequences of SARS-CoV-2, the virus that causes COVID-19. That generates antigens of the virus’s signature spike protein, in turn prompting an immune response.
A single injection of either of the AAVCOVID vaccine candidates induced neutralizing antibodies in one mouse model of obesity and another of aging—two conditions that have been linked with poor COVID-19 outcomes. The response lasted for at least three months, according to the study. In the monkey models, the immune response lasted for five months.
All animals also showed memory T-cell responses, which are believed to be critical for maintaining long-term immunity to COVID-19.
Although the demand for the mRNA vaccines from Pfizer and Moderna is strong, the shots present some hurdles. The need for cold storage will make distributing the vaccines in developing countries difficult. And both vaccines require two doses to confer full immunity, which only adds to the logistical challenges—and the cost—the Mass Gen researchers argued in their study.
Because AAVs are already widely used to deliver gene therapies like Novartis’ Zolgensma for spinal muscular atrophy, the Mass Gen team was able to ramp up its preclinical studies quickly. To accelerate the effort, the researchers formed early partnerships with gene therapy specialists at the University of Pennsylvania and with Novartis, which agreed to manufacture the AAVCOVID vaccines for clinical trials.
“The fact that there’s an established industry out there around AAV made it easy for us to step into the existing [manufacturing] capacity, rather than having to build it,” said lead investigator Luk Vandenberghe, Ph.D., an associate professor at Harvard Medical School and director of the Grousbeck Gene Therapy Center at Massachusetts Eye and Ear, in an interview with Fierce Biotech last year.
Vandenberghe’s team is now planning to start clinical trials of the vaccines overseas.
The researchers acknowledged in the study that several other vaccine candidates are nearing approval. But they believe the AAVCOVID shots will prove valuable because of other attributes that “will likely be critical to achieving the desired long-lasting herd immunity at a global population scale,” they wrote. “Many of these considerations are logistical in nature and seek to reduce the cost, time, and complexity of vaccine distribution using available infrastructure around the world.”