Unlocking New Therapies after COVID Vaccines

The mRNA vaccine technology now in widespread use in new COVID-19 vaccines is built on research at Penn Medicine. It has extraordinary potential in the prevention and treatment of numerous intractable diseases.

The spike protein is the entry key for a coronavirus to attach to and infect a human cell. But when the body can make that key for itself, it can learn to lock the virus out. Such is the promise of the first two COVID-19 vaccines produced by Pfizer/BioNTech and Moderna.

Man looking at a vital of fluidThe week before both vaccines were approved by the Food and Drug Administration for emergency use in December 2020, the Washington Post editorial board lauded the remarkable science behind them — and two major advances in that science begun decades ago at Penn—as “an extraordinary advance in technology, never before used on such a scale, with great promise for the future, and some uncertainties.”

These vaccines involve injecting modified synthetic messenger RNA (mRNA) molecules that code for the SARS-CoV-2 spike protein into the body. The cells use the mRNA as a template to build the spike protein to which the body then mounts an immune response to learn to fight the virus, should it ever encounter the real thing.

It is the first time approved human vaccines have used mRNA to teach the body to make viral proteins, rather than introducing a viral protein or weakened virus itself to prime the immune system as in most traditional vaccines. The vaccines are new — but the technology has been long in development. And now mRNA has a promising future for countless new vaccines and therapies.

The vaccine’s story begins in the early 2000s, when Drew Weissman, MD, PhD, a professor of Infectious Diseases at the Perelman School of Medicine, and Katalin Karikó, PhD, an adjunct associate professor, began working together at Penn. One major advance they made was to modify the mRNA molecule itself so that it could avoid attack from the immune system and the inflammatory response in the body that was seen in early animal studies. The other advance was enclosing the mRNA in a lipid nanoparticle envelope to deliver mRNA safely and efficiently into the body — a delivery mechanism that is already part of multiple approved drugs at higher concentrations and one that, fortuitously, turned out to also function as an adjuvant to enhance the effectiveness of the COVID-19 vaccines.

The discovery has been hailed by some as Nobel Prize-worthy. “If anyone asks me whom to vote for some day down the line, I would put them front and center,” Derrick Rossi, PhD, co-founder of Moderna, told STAT News. “That fundamental discovery is going to go into medicines that help the world.”

Penn Medicine scientists first began exploring the possibility of using mRNA vaccines for HIV more than 20 years ago, and in recent years have turned to developing them for malaria, influenza, and other infectious diseases. Cancer immunotherapy researchers are investigating ways to make personalized cancer “vaccines.”

In Weissman’s lab at Penn, he and Norbert Pardi, PhD, a research assistant professor, are developing new mRNA vaccines for 30 different infectious diseases. Five are already being tested in humans — against HIV, the genital herpes virus, and the influenza virus. The team is also involved in a clinical trial for a universal flu vaccine to replace an annual one.

Weissman also anticipates opportunities to develop pan-coronavirus vaccines to address not only newer variants of SARS-CoV-2, but also any future related viruses that may cross over into humans from other species — a possibility to take seriously, considering that it has happened three times in the last 20 years, with SARS, MERS, and the current pandemic.

Therapeutic uses of mRNA are yet another new possibility opened by the success of the platform in COVID-19 vaccines. The same technology could be used as a basis for gene therapies that could target stem cells and fix genetic mutations, or as a treatment method for acute and chronic diseases — enabling the body to produce therapeutic proteins within specific organs or cell types where they are needed.

‘I Got the Shot’: COVID-19 Vaccine Arrives at Penn Medicine

Woman holding a vaccine shotAfter wrapping up his night shift at 6:15 a.m. on December 16, 2020, Emergency Department nurse Eric Young, RN, BSN, was the first to receive the COVID-19 vaccine at Pennsylvania Hospital — marking what many saw as the “beginning of the end” of the pandemic at Penn Medicine.

Within a month, Penn Medicine had administered over 43,000 doses of the Pfizer/BioNTech and Moderna vaccines.

Faculty and staff from Penn Medicine were eager to share their excitement and confidence in the science behind the vaccines’ effectiveness and safety. In a series of posters, screensavers, and internal messages, dozens proudly proclaimed “I Got the Shot,” explaining their reasons for being vaccinated and urging others to do the same. Concurrently, Black faculty and staff have spearheaded efforts to address vaccine hesitancy that remains particularly widespread among people of color. According to a December 2020 survey by the Kaiser Family Foundation, more than a quarter of the American public overall (27 percent) and 35 percent of Black adults say they probably or definitely would not get the vaccine.

The goal among these Penn Medicine vaccine ambassadors? To support, educate, and be responsive to questions and concerns among colleagues and patients who may be more hesitant to receive a new vaccine — and ultimately to bring a swifter end to the pandemic.

Coming Together on the Hospital of the University of Pennsylvania Campus

New hospital skywalkThis fall, steel frames for two bridge structures were assembled on the ground and lifted into place, connecting the buildings of the Hospital of the University of Pennsylvania (HUP). The new Pavilion (HUP East) will ultimately be connected to HUP West through one of these new bridges and an underground tunnel that span 33rd and 34th Streets, and to the Perelman Center for Advanced Medicine through two bridges above Convention Avenue. A fourth, open-air pedestrian walkway will connect to SEPTA’s Penn Medicine Station.

Sterile Goes Big

Interventional Support CenterPenn Medicine’s new Interventional Support Center (ISC) opened in February and is now the centralized hub for processing instruments from both the Hospital of the University of Pennsylvania (HUP) and Pennsylvania Hospital. At nearly 110,000 square feet, it is the largest instrument processing and supply picking facility in the country, supporting up to 250 surgical cases each day.

Clean instruments are a crucial element of patient safety. By centralizing processing from multiple hospitals at this new facility with plans to include the Pavilion (HUP East) and potentially more hospitals in the future, Penn Medicine can ensure consistent, state-of-the-art processing that complies with evolving standards.

Employee well-being has been a central tenet in the facility’s design. Ergonomic features include height-adjustable decontamination sinks and a rotating storage rack — analogous to the device that rotates clothing to move it through a dry cleaner’s — to deliver instrument trays to workstations without requiring staff to reach or bend as they would with traditional racks.

Jameson Takes Helm of AAMC Board

Headshot of Larry JamesonIn November, J. Larry Jameson, MD, PhD, executive vice president of the University of Pennsylvania for the Health System and dean of the Perelman School of Medicine, became the new chair of the Board of Directors for the Association of American Medical Colleges (AAMC). Jameson has been a member of the AAMC Board of Directors since 2017, and during that time also served as chair of the AAMC Council of Deans. The AAMC, a not-for-profit association dedicated to transforming health through medical education, health care, medical research, and community collaborations, leads and serves America’s medical schools and teaching hospitals.

Jameson assumes this new national leadership role while continuing to lead at Penn Medicine. In December, University of Pennsylvania President Amy Gutmann, PhD, announced the extension of Jameson’s term through June 30, 2025. He came to Penn Medicine from his post as dean of the Feinberg School of Medicine and Vice President of Medical Affairs at Northwestern University in 2011.

“As we continue confronting a global pandemic and envisioning our future as a University and a society, Larry’s leadership of Penn Medicine and the Perelman School coupled with his consummate university citizenship are universally praised and admired,” Gutmann said.

Among the many markers of Jameson’s service as executive vice president and dean that Gutmann cited are the growth in both quality and diversity of PSOM’s faculty, staff, and students; the strength of both educational and research programs; strong financial performance and fundraising; improvements to facilities and infrastructure; and important and measured growth of the health system. Gutmann also specifically lauded Jameson’s efforts to advance diversity, equity, and inclusion across Penn Medicine and the University.

A New Public Health Campus in West Philadelphia

Mercy HospitalPenn Medicine has joined forces as part of a coalition of the region’s premier health care organizations transform Mercy Philadelphia Hospital at 54th and Cedar Ave. into a thriving, reimagined campus that will provide high-quality, community-informed health care and services centered on the public health needs of the facility’s West Philadelphia neighbors.

Coalition partners — Public Health Management Corporation (PHMC), Penn Medicine, Trinity Health Mid-Atlantic, and Independence Blue Cross — plan to develop a campus focused on health equity. Its operations will rely heavily on a patient-centered approach to high-quality medical care, behavioral health, and social services. Children’s Hospital of Philadelphia (CHOP) is also exploring the option to offer pediatric behavioral health services on the campus. Penn Medicine plans to take over operation of emergency and acute care services on the campus in late March.

“The COVID-19 epidemic has underscored the necessity of working together past the walls of individual institutions,” said Kevin B. Mahoney, CEO of the University of Pennsylvania Health System. “Collaboration and bringing together diverse expertise is the best way to make a difference for our communities.”

While some acute care beds will be retained to support the emergency department, providers will work to connect patients to primary and community care providers. Unlike the recent closure of Hahnemann Hospital, which remains a stark example of the perils of any wind-down process, the coalition partners will provide an array of medical, behavioral and social service program options that will maintain — and ultimately improve — community access to care, while retaining jobs and ensuring the reimagined Mercy campus is a thriving center of activity.

PHMC, Penn Medicine, and Independence Blue Cross will explore community partnerships to identify supplemental offerings to address key community issues, such as food insecurity, health and wellness education, and activities to support the community.

Filtering Bias Out of Kidney Testing

Q&A with Nwamaka Eneanya, MD, MPH, on Advancing Health Equity and Removing Race from Assessment of Renal Function — a Driver of Disparities in Timely Access to Care

Read the full Q&A here.

Penn Medicine’s Steps to ACT on Diversity, Equity, and Inclusion

animated silhouettes of peopleP^^^enn Medicine’s Action for Cultural Transformation (ACT), officially launched on July 1, 2020, is an ongoing extensive institutional effort to ensure equity, mitigate bias and eliminate racism at Penn Medicine. The Office of Inclusion and Diversity (OID), in partnership with representatives from across the institution, has been working to chart the course for ACT to bring substantive change. Within weeks of launching the ACT effort, Penn Medicine departments, centers, and entities identified dozens of new, impactful, inclusive, and sustainable actions to pursue immediately as “Just Do It” goals. Meanwhile, longer-term strategic planning for the full, comprehensive effort was underway, engaging thousands of faculty, staff, and students in the effort.

The strategy and implementation plan was released on the OID website this winter and is publicly available at www.med.upenn.edu/inclusion-and-diversity.

“The charge to ACT is clear,” said Eve J. Higginbotham, SM, MD, ML, vice dean for Inclusion and Diversity in the Perelman School of Medicine, and Dwaine Duckett, senior vice president for Human Resources at the University of Pennsylvania Health System, in announcing the plan. “We aim to eliminate structural injustice across Penn Medicine and the communities we serve to achieve our vision for the future: Penn Medicine is united as an anti-racist, equitable, diverse and inclusive organization.”

A Bard for Health Equity Leads Family Medicine and Community Health Department

Headshot of Richard WenderRichard Wender, MD’79 is in his element. “COVID virus has exposed unjust disparities,” he sings with gusto to the virtual audience on the other side of his computer screen. “We join as one to raise our voice as NCCRT...We will screen you. We will screen you.” Anyone fortunate enough to attend the annual meeting of the National Colorectal Cancer Roundtable can look forward to a musical performance by the Chair, and this year’s virtual meeting was no exception. “We Will Screen You” was Wender’s adaptation of Ragtime’s “Make Them Hear You” to reaffirm the medical community’s commitment to providing preventive care during the COVID-19 pandemic. If Wender had not become a professor and physician, he might have taken his lyrical prowess to the stage.

Broadway’s loss is Penn Medicine’s gain. As Wender settles into his new role as chair of Family Medicine and Community Health in the Perelman School of Medicine, he has already made an impression with his quick wit and empathetic nature. After joining Penn in August 2020, he spent his first several months on the job scheduling one-on-one conversations with every faculty member and nurse practitioner in the department. “I’m very much a believer in creating a loving, supportive culture,” he says.

Prior to joining Penn Medicine, Wender served for 12 years as chair of Family and Community Medicine at Thomas Jefferson University, where he helped catalyze the creation of the Division of Geriatric Medicine and a Palliative Care program. Wender also served as the first ever Chief Cancer Control Officer for the American Cancer Society. As his job titles and areas of responsibility have changed, the themes of health equity and social justice have permeated his life’s work.

Wender joins Penn Medicine at what he calls an “extraordinary moment in health care,” a confluence of events that has exposed the gaping inequity in health access and outcomes. “In an environment of national disunity and racial injustice arose a pandemic that has not only exposed disparities but helped people understand how they came about,” he reflects.

Wender has long pointed to social determinants of health — factors like household income, educational attainment, and workplace safety — to explain why certain populations experience worse health outcomes than others. “What we’ve now realized is that structural racism is one of the most important social determinants of health,” he says.

An inextricable link between primary care and the goal of equity are at the core of his commitments both to growing Family Medicine and Community Health and to working with other departments within Penn Medicine to expand primary care access in West Philadelphia and beyond. “We have a crucial role to play as an anchor institution in our city and neighborhood,” he says. Yet when it comes to social determinants of health, Wender also sees Penn Medicine’s role as one voice in a larger chorus. “Health care providers, try as they might, can’t carry the act alone.”

He is enthusiastic about taking the stage to play his part.

“One of the primary reasons I came to Penn Medicine is because my new colleagues are deeply committed to grappling with issues of social justice,” he says. “The holistic pursuit of health equity is in their DNA.”

— Ashley Rabinovitch

Research Reveals...

From basic science to public health, discovery at Penn Medicine is constantly unveiling answers to key questions that can lead to better treatments for disease and prevention of harm. Below are just a handful of recent examples.

Looking down a gun barrelHow many firearm injuries are there in total? A study published in JAMA Internal Medicine showed that there are about 329 firearm injuries each day in the U.S., or about two nonfatal injuries for every firearm-related death. The study signifies the importance of evaluating firearm prevention policies that address these more common cases where victims survive, in addition to preventing deaths.

Telemedicine meetingDoes telemedicine equitably expand access to care? Older patients as well as minorities, non-English speakers, and those with lower incomes faced inequities in accessing care during the spring of 2020 when many in-person visits were shifted to telemedicine during the initial COVID-19 surge, according to an analysis published in JAMA Network Open. Recognizing and addressing barriers will be crucial to implementing virtual care strategies that benefit all patients, the researchers say.

Microscopic view of T cellsWhere do (and don’t) killer T cells go? So-called “killer” T cells, the immune cells that recognize and destroy other cells that have a particular target they are trained to attack, normally do not migrate out of the bloodstream. By analyzing samples from both blood and lymph — a whitish, watery fluid that flows between tissues and organs and the bloodstream — the researchers were able to catalogue the detailed molecular characteristics of T cells collected from both fluids in the same subjects, for the first time. The findings, published in Cell, could help explain why therapies that use modified killer T cells do not work well against solid tumors, among other medical mysteries.

Microscopic view of Cytokine StormWhat is a cytokine storm? In the New England Journal of Medicine, Penn Medicine researchers published a unifying definition of “cytokine storm” as a framework to assess and treat severely ill patients whose immune systems have gone rogue — something that has become a major challenge with COVID-19. Characteristics of a cytokine storm in their definition include elevated circulating cytokine levels, acute systematic inflammatory symptoms, and a secondary organ dysfunction beyond what could be attributed to a normal response to a pathogen.

Microscopic view of cellsWhat transforms a normal cell into a cancer cell? Two universal metabolic pathways may tie together the means by which cancer arises in cell types all over the body, according to a study published in Cell Metabolism. The two key elements: antioxidant defense and nucleotide synthesis.

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