Henry Daniell, PhD, of Penn Dental Medicine has received a grant from Pennsylvania’s COVID-19 Vaccines, Treatments and Therapies (CV-VTT) program to support coronavirus research.
“We are thrilled to see this commitment from the state of Pennsylvania in our collective battle against COVID-19,” said Mark S. Wolff, DDS, PhD, Penn Dental Medicine’s Morton Amsterdam Dean. “Dr. Daniell’s research through his unique plant-based platform holds the potential for transformative application.”
Daniell, the WD Professor in the Department of Basic & Translational Sciences, received 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 collaboration with Kenneth Margulies, MD, of Penn’s Perelman School of Medicine, Daniell is pursuing first-in-human studies of an oral preparation that directly supplements two beneficial proteins that are severely depleted in COVID-19 patients, ACE2 and its protein product, angiotensin (1-7). They will study whether a drug developed for 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. Daniell’s earlier preclinical studies in PAH animal models showed that orally delivered ACE2 made in plant cells accumulated 10 times more in the lungs than in the blood and safely treated PAH. His proposed clinical studies would explore whether oral supplementation of ACE2 and angiotensin 1-7 can help mitigate complications of COVID-19.
“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,” said Daniell, “few are endeavoring to specifically target the pathophysiologic mechanisms invoked by COVID-19 infection, which is what we plan to do.”
Daniell also 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,” said 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.”
To evaluate his vaccine in rhesus macaque monkeys, Daniell will collaborate with Jay Berzofsky, MD, PhD, chief of the Vaccine Branch at the Center for Cancer Research at the National Institutes of Health.
For the therapeutic and vaccination strategies, 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.
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