Philadelphia — Penn Dental Medicine is among the 23 state-wide awardees from the administration of Pennsylvania Governor Tom Wolff to advance coronavirus research. The award to the lab of Dr. Henry Daniell, W.D. Miller Professor in the Department of Basic & Translational Sciences, is part of $10 million in grant funding through the state’s COVID-19 Vaccines, Treatments and Therapies (CV-VTT) program to support the rapid advancement of vaccines, treatments, and therapies.
“We are thrilled to see this commitment from the state of Pennsylvania in our collective battle against COVID-19,” says Penn Dental Medicine’s Morton Amsterdam Dean, Dr. Mark S. Wolff. “Dr. Daniell’s research through his unique plant-based platform holds the potential for transformative application.”
Dr. Daniell was awarded just over $823,000 to accelerate the progress of two novel strategies for combating COVID-19, both of which leverage decades of experience with the successful development of plant-based protein therapies to develop targeted oral therapeutics and vaccination strategies.
In the therapeutic realm, Dr. Daniell, in collaboration with Dr. Kenneth Margulies of Penn’s Perelman School of Medicine, is pursuing first-in-human studies of an oral preparation that directly supplements two beneficial proteins — ACE2 and its protein product, angiotensin (1-7) — that are severely depleted in COVID-19 patients. It will assess whether a drug developed for a very different condition— pulmonary arterial hypertension (PAH) — could reduce lung and heart injuries in coronavirus patients.
Reduced ACE2 expression has been linked to acute respiratory distress, severe lung injury, multi-organ failure and death, especially in older patients. Dr. Daniell’s earlier preclinical studies in PAH animal models showed that orally delivered ACE2 made in plant cells accumulated ten times higher in the lungs than in the blood and safely treated PAH. His proposed clinical studies through this grant award would explore whether oral supplementation of ACE2 and angiotensin-1-7 can help mitigate complications of COVID-19 disease.
“Due to the rapid evolution of the COVID-19 pandemic, most therapeutic strategies being explored to mitigate the severe respiratory and extrapulmonary pathology caused by COVID-19 infection involve the repurposing of antiviral therapies that have been developed for other viral infections,” explains Dr. Daniell, “few are endeavoring to specifically target the pathophysiologic mechanisms invoked by COVID-19 infection, which is what we plan to do.”
In the vaccination realm, Dr. Daniell is developing a plant-based oral vaccination to induce durable mucosal immunity suitable for boosting waning immunity following an injected vaccine. “Amidst an explosion of vaccine development efforts, virtually all COVID-19 vaccination strategies are employing injectable vaccines that will produce systemic immunity, but will not promote mucosal immunity,” says Dr. Daniell. “Mucosal immunity is required to protect at viral entry ports and to be more durable and effective in patients with compromised immune systems due to advanced age or comorbidities.” For evaluation of his vaccine in Rhesus Macaque monkeys, Dr. Daniell will collaborate with Dr. Jay Berzofsky, Chief, Vaccine Branch, Center for Cancer Research, National Institutes of Health.
For both the therapeutic and vaccination strategies, Dr. Daniell is pursuing strategic, short-term funding — like the CV-VTT grant — to enable augmented infrastructure and preliminary safety and efficacy data that will position both strategies for further funding from federal and/or commercial entities.
The CV-VTT program was made available to Pennsylvania-based entities that demonstrate both a financial need and a well-defined pathway to the accelerated commercialization of a new vaccine, treatment, or therapy in direct response to COVID-19. Dr. Daniell’s award was the larger of two awards within the University of Pennsylvania (view full recipient list).
Funding for the program was appropriated from the Act 2A of 2020, known as the COVID-19 Emergency Supplement to the General Appropriation Act of 2019, to the Pennsylvania Department of Health (DOH), to be administered through a Notice of Subgrant by the Pennsylvania Department of Community and Economic Development’s (DCED) Office of Technology and Innovation.