Potential Vaccine Against COVID-19 Shows Early Promising Results in Peer-reviewed Research

UPMC Active in Italy, Through the ISMETT-Ri.MED Cluster, to Face the Emergency in Terms of Care and Research Alongside the Sicilian Region

PITTSBURGH, April 2, 2020 – Scientists at the University of Pittsburgh School of Medicine today announced a potential vaccine against SARS-CoV-2, the novel coronavirus that causes the current COVID-19 pandemic. Early tests in the mouse model showed that the vaccine, administered through a fingertip-sized patch, produces antibodies specific to the new SARS-CoV-2 coronavirus in quantities deemed sufficient to neutralize the virus.

The article, which appeared in EBioMedicine, a journal published by the Lancet, is the first study to be published following review by scientists from other institutes and describes a potential vaccine against COVID-19. The researchers were able to act quickly as the foundations had already been laid thanks to previous work during previous coronavirus outbreaks.

"We have worked in the past with the SARS-CoV outbreak in 2003 and MERS‐CoV in 2014. These two viruses, closely related to SARS-CoV-2, teach us that a particular protein, called spike, is important for inducing immunity against the virus. We knew exactly where to fight this new virus," said Andrea Gambotto, M.D., co-senior author – formerly in the Department of Molecular Genetics and Biochemistry at the University of Pittsburgh – who has always been involved in vaccine research. "That's why it's important to fund vaccine research. You never know where the next pandemic will come from."

"Our ability to rapidly develop this vaccine is the result of collaboration between scientists with expertise in different research areas working with a common goal," continued Louis Falo, M.D., Ph.D., co-senior author and professor and director of the Department of Dermatology at the University of Pittsburgh School of Medicine and UPMC.

Compared to the other potential experimental mRNA vaccine on which clinical trials have just begun, the vaccine studied at the University of Pittsburgh, which the authors have christened PittCoVacc, short for Pittsburgh CoronaVirus Vaccine, follows a more established approach, using laboratory-created viral protein fragments capable of developing immunity. Current flu vaccines work similarly.

The researchers also used an innovative approach to administer the vaccine based on the use of a micro-needle vector, which increases its potency. It is a patch the size of a fingertip with 400 tiny needles that administer fragments of the spike protein through the skin, where the immune reaction is strongest. The device is used as a normal patch and the micro-needles, made entirely of glucose and protein fragments, dissolve in the epidermis.

'We relied on the skin scarification method originally used to administer the smallpox vaccine, but employing a high-tech version that is more efficient and reproducible from patient to patient,' said Dr Falo. "And it's also quite painless, much like the feeling of Velcro on the skin."

The system is also highly scalable. The protein fragments are made by a cell factory with layers upon layers of cultured cells designed to express the SARS-CoV-2 spike protein and which can be further stacked to multiply its yield. Protein purification can also be carried out on an industrial scale. The mass production of micro-needles involves mixing proteins and sugars in molds using a centrifuge. Once produced, the vaccine can remain at room temperature until it is used, eliminating the need for refrigeration during transport or storage.

'For most vaccines it is not initially necessary to address the issue of scalability,' explained Dr Schmidt. Gambotto, "but when trying to quickly develop a vaccine against a pandemic, this is the first necessary condition."

After being tested on mouse models, it was noted that PittCoVacc generated a large amount of antibodies against SARS-CoV-2, and all this happened within two weeks of applying the patch.

Animal models have not yet been evaluated over the long term, but the researchers point out that mice given the MERS-CoV vaccine have produced a sufficient level of antibodies to neutralize the virus for at least a year, and so far antibody levels in models vaccinated against SARS-CoV-2 seem to follow the same trend.

It is important to underline how the vaccine with micro-needle patch against SARS-CoV-2 maintains its power even after sterilization with gamma rays, a fundamental step towards the creation of a product suitable for use in humans.

The authors have submitted an application for approval of an investigational new drug (IND) to the Food and Drug Administration in anticipation of initiating a phase I clinical trial in humans in the coming months.

'Clinical trials on patients typically take at least a year and probably longer,' said Dr. Smith. Falo, "the particular situation we are experiencing is new and unprecedented, so we do not know how long the clinical development process will take. Recent revisions to normal processes suggest the possibility of rapid progress."

The other authors of the study are Eun Kim, Geza Erdos, Ph.D., Shaohua Huang, Thomas Kenniston, Stephen Balmert, Ph.D., Cara Donahue Carey, Michael Epperly, Ph.D., William Klimstra, Ph.D. and Emrullah Korkmaz, Ph.D. of the University of Pittsburg; and Bart Haagmans of Erasmus Medical Center.

The study was funded by the National Institute of Allergy and Infectious Diseases, the National Institute of Arthritis and Musculoskeletal and Skin Diseases, and the National Cancer Institute.

Prof. Bruno Gridelli, Executive Vice President of UPMC International and Country Manager of UPMC in Italy underlined: "UPMC Italy, with ISMETT IRCCS and the Ri.MED Foundation, is committed to supporting the Sicilian Region in addressing the COVID-19 emergency both in terms of care and research. The important advances in research conducted in Pittsburgh by researchers at the University of Pittsburgh and UPMC are among the important benefits of the international partnership of the ISMETT-Ri.MED cluster."

UPMC and the University of Pittsburgh are planning a virtual press conference today at 5 p.m. For more information visit the website www.upmc.com/media The media will also be able to share the live streaming of the press conference through this link: public livestream of the virtual press conference.