Skip to main content

Tag: Patel

A Wistar Journey Through the Past, Present, and Future of Immunization Work

Vaccines are a crucial public health tool in its’ arsenal against diseases. Resurgences of diseases long thought eradicated are popping up decades later in sewage waters here and abroad, and we’ve witnessed what the impact of war has on countries whose health systems have crumbled under the ravages of war—we are not as far removed as we’d like to be from diseases once prevented by vaccines. With more than half a century of basic research for vaccine development, The Wistar Institute plays an integral role in immunization around the globe.

Rubella, rabies, and rotavirus. Wistar scientists developed vaccines for these diseases that are used in immunization programs worldwide. The rubella vaccine by Wistar scientists effectively ended the pandemic in the United States, as declared by the CDC in 2005. Two rabies vaccinations developed from the Institute addresses the disease in both animals and humans. In 2006, Wistar and collaborators created a rotavirus vaccine which became part of the regular immunization schedule for U.S. babies and is used or approved in over 45 countries. And we’re just getting started.

“Immunization is possibly one of the most impactful medical interventions ever developed. Millions of lives are saved each year by vaccination, and we live healthier and longer lives due to vaccines.” states David Weiner, Ph.D., Executive Vice President, Director of Wistar’s Vaccine & Immunotherapy Center, and W.W. Smith Charitable Trust Professor in Cancer Research, in the Immunology, Microenvironment & Metastasis Program at Wistar’s Ellen and Ronald Caplan Cancer Center.

This National Immunization Awareness Month, we have shared a few snapshots of current vaccine development projects at the Institute as well as what these researchers’ hopes are for the future of immunization.

Tackling Both Infectious Disease and Cancer with Immunization

Dr. Weiner’s research takes on both infectious disease and cancer. His work encompasses developing new ways to build and deliver synthetic nucleic acid vaccines – particularly advancing a new approach that drives self-assembly of an antigen into a more potent vaccine inside a vaccinated person. This approach gives the body the genetic information to become the factory to create the vaccine. Furthermore, his lab is developing new types of cancer therapeutic vaccines with the goals of creating strong anti-cancer immunity and eradicating cancer cells.

Weiner’s collaborations with public and private institutions is centered around novel immunization technology developed from his lab called DNA-encoded monoclonal antibodies (DMAbs) against diseases such as COVID-19, Zika, and Ebola.

Regarding the future, he shares, “Together with our collaborators, we hope to move new prototype HIV vaccines into human clinical trials later this year, and continue to advance vaccines for emerging pathogens, as well as cancer immunotherapies.”

Developing DNA Vaccines

Ami Patel, Ph.D., Caspar Wistar Fellow in the Vaccine and Immunotherapy Center, focuses her scientific efforts on DNA vaccines which have potential to be more stable and economical over traditional vaccine production. “We are trying to understand how different vaccines work in the body. How do vaccines generate different types of immune responses and can we use this to understand protection against infectious diseases. We are using this information to help develop the next generation of potential vaccines.” she says.

Patel emphasizes the importance of vaccines for young children and adults by calling back to various infectious diseases like polio that are no longer very common because of immunization. “Vaccines help protect us against serious disease. Some of us remember the discomfort of chicken pox as children. There is now a vaccine.”

While she calls the COVID-19 pandemic “devastating to global health”, Patel also recognizes the pandemic’s challenges proved fertile ground for an extraordinary collaborative time for biomedical scientists. “My hope is for vaccine researchers across different disciplines to continue to work together to help us understand different infectious diseases and develop better vaccines.”

Zooming in on a Nanoscale

In collaboration with Weiner, Daniel Kulp, Ph.D., associate professor in the Vaccine and Immunotherapy Center, has embraced nanotechnology in his vaccine research. “We are developing rationally engineered nanoparticle vaccines that can elicit extremely broad coronavirus immunity providing a proof-of-concept that a pan-coronavirus vaccine is possible,” Kulp elaborates.

While the Kulp laboratory is developing several promising vaccines, he emphasizes that his goal is to assess these candidates in humans. He says, “We are working to reduce barriers for launching small experimental medicine clinical trials allowing for broader evaluation of our best vaccine concepts. Through this type of work, I have high hopes that our generation can claim credit for the eradication of SARS-CoV-2.”

Kulp expresses that “Vaccines are one of the single most effective medical technologies humans have developed saving hundreds of millions of lives. Vaccines do not work without immunizations. This message is incredibly important.”

Expanding the Caspar Wistar Fellows Program

The Caspar Wistar Fellowship is a model for recruiting the best and brightest junior scientists to Wistar where they can build scientific networks and advance their unique independent research programs.

Two years ago philanthropists Doug and Peggy Briggs established the Caspar Wistar Fellowship to attract the most talented junior scientists from across the nation and beyond, and jumpstart their scientific careers. Put at the center of a collaborative nexus of bold and distinguished scientists working in cancer and infectious disease research at Wistar, What can they achieve?

“If we can find the best and brightest junior scientists, I believe we can move their careers along much faster,” said Doug. “They have the potential, and we are giving them a leg up and hopefully more responsibility than even they think they are ready for.”

These supremely driven and curious scientists have a lot on their shoulders, but have the focus, education and courage to become our next generation of scientific leaders.

Dr. Daniel Claiborne, Wistar’s newest Caspar Wistar Fellow, joins the Fellowship from the Ragon Institute of MGH, MIT and Harvard where he is trying to better understand T cells and CAR T cells for the treatment of HIV. CAR T cells, called chimeric antigen receptor T cells, are patient-derived T cells that have been engineered to target and destroy a specific antigen on the surface of a cancer cell. They are considered “super charged” immune cells that act like a living drug, latching onto a tumor cell to terminate it. CAR T cells have been developed as an immunotherapy for cancer, but Dr. Claiborne wants to explore their potential against HIV.

“This is a huge opportunity to start my own lab so there is some trepidation, but it’s what I’ve been working towards for 13 years, so I’m also very motivated as well,” says Dr. Claiborne. “The recent publications I worked on were not the end, but the beginning in our effort to understand the hurdles in repurposing CAR T cells for HIV. We learned a lot about what these cells can and cannot do. The big question in the field is, ‘Why do CAR Ts stop working?’ It’s an open-ended question and a ton of research has already been done.”

Dr. Claiborne brings an entirely different perspective to CAR T research that will enhance our basic understanding of CAR T cells and help inform their use in oncology and immunotherapy.

“The thing we do differently is use a humanized mouse model that carries a functional human immune system,” said Dr. Claiborne. “This is a malleable small animal model with actual human cells and T cells so we can learn more about what makes our CAR T therapies fail. And that’s largely translatable to more than just HIV infection. It informs basic T cell biology and illuminates what makes T cells do their job or not in many chronic disease states. The ability to do that in a small animal model with a human immune system is powerful and one step closer to the question we all think is important: What causes T cells to lose their function.”

Dr. Ami Patel became Wistar’s second Caspar Wistar Fellow in 2020 and has lived a pretty incredible year with lots of big changes. Since the start of the pandemic, Dr. Patel has been a key leader in the SARS-CoV-2 vaccine and immunotherapy efforts at the Vaccine & Immunotherapy Center.

“In September, I became a Caspar Wistar Fellow and then a week later, I went on maternity leave,” said Dr. Patel. “I truly appreciate this opportunity and it’s exciting to pursue my own independent research. I have multiple new experiments in which to design and develop new ideas. And I’m at the early stages building my lab and getting it up and running.”

Dr. Patel was recruited to the program after shining in the lab of Wistar’s Dr. David Weiner, first as a postdoctoral fellow and associate staff scientist. She was appointed as research assistant professor in 2019.

“As a Caspar Wistar Fellow, my new independent research program is focused on understanding the cellular and immune mechanisms associated with vaccine and immunotherapy delivery and using this information to improve the next generation of vaccines against emerging pathogens that could be tomorrow’s next major outbreaks. This is a great opportunity to explore new strategies,” she says.

As she is establishing her research program, Dr. Patel is hiring her own team to manage projects that run the gamut of emerging pathogens.

“Now is the time to put my new ideas to the test and drill down on key independent experiments that will lay the foundation for my research,” Dr. Patel added.

For Dr. Rahul Shinde, Wistar’s inaugural Caspar Wistar Fellow, this stage of independence has brought a myriad of research collaborations. His work focuses on pancreatic cancer and how cancer hijacks immune cells called macrophages, which normally stimulate the immune system and destroy cancer and pathogen invaders. Dr. Shinde is trying to elucidate when and how macrophages shift their function from fighting cancer to doing cancer cells’ bidding in the tumor microenvironment. He is also interested in the gut microbiome and its connection with modulating tumor progression.

“It has been great at Wistar, and such a positive feeling setting up my lab and working to publish,” said Dr. Shinde. “I feel lucky to collaborate with Wistar principal investigators across research fields including autoimmune diseases such as lupus. I’m also exploring pancreatic cancer’s tumor microenvironment that fosters cancer growth and therapy resistance. I’ve been part of several projects making interesting observations.”

Doug Briggs believes giving strong, sharp-minded scientists a platform to launch their careers is most important.

“Bringing these early-career, star scientists along faster in their careers is helping push the biomedical research dial forward. There are big up sides — for us all — with more and faster success in science,” says Doug.

“For Doug and Peggy Briggs to stand up and create this opportunity is very motivating, especially for scientists who do high-risk and out-of-the-box research,” said Dr. Claiborne. “It’s a huge deal. Pursue your ideas and see where they take you.”

The Caspar Wistar Fellowship will continue to boost the potential in early-career scientists it brings to Wistar. With each new Fellow who calls Wistar home, Doug and Peggy’s straightforward belief becomes a more powerful engine for expanding research and pushing the Institute to succeed.

Stay tuned for the fourth Caspar Wistar Fellow to be recruited very soon!

Latest Wistar Discoveries: Fine-tuning Vaccine Delivery in Preclinical Models to Advance MERS DNA Vaccine Candidate and Discovering New Targets for Cancer Therapy

A team of Wistar scientists led by Dr. David Weiner, Wistar executive vice president, director of the Vaccine & Immunotherapy Center and W.W. Smith Charitable Trust Professor in Cancer Research, and Dr. Ami Patel, Caspar Wistar Fellow, and collaborators have developed a synthetic DNA vaccine candidate for Middle East respiratory syndrome coronavirus (MERS-CoV).

A vaccine candidate based on their research was shown to be safe and tolerable in a recently completed human phase 1 study with a three-dose intramuscular injection regimen and is currently in phase 1/2a trial.

Our scientists continue to expand the preclinical studies of the vaccine in support of its clinical development. They have now tested intradermal delivery using a shortened two-dose immunization schedule in non-human primates (NHP).

“Low-dose delivery and shortened regimes are crucial to rapidly induce protective immunity, particularly during emerging outbreaks, as the current SARS-CoV-2 pandemic has emphasized,” said Weiner.

In a paper published in the journal JCI Insight, he and colleagues reported that low-dose intradermal administration induces potent immunity and protects from virus challenge. The low-dose regimen with intradermal delivery was more impactful in controlling disease and symptoms than the higher dose given intramuscularly.

“Intradermal delivery of synthetic DNA vaccines has significant advantages for rapid clinical development. It can be dose sparing and has higher tolerability in people compared with intramuscular injection,” said Patel.

Their experience developing this MERS vaccine candidate helped the team advance a COVID-19 vaccine through clinical trials in a short time.

Vaccine candidates that are simple to deliver, well tolerated, and can be readily deployed in resource-limited settings will be important to achieve control of infection for coronaviruses and other emerging infectious diseases.

The lab of Dr. Rugang Zhang, deputy director of The Wistar Institute Cancer Center, Christopher M. Davis Professor and leader of the Immunology, Microenvironment & Metastasis Program, studies the process of cellular senescence and the changes in gene expression that accompany it.

Cellular senescence is a stable state of growth arrest in which cells stop dividing but remain viable and produce an array of inflammatory molecules collectively defined as senescence-associated secretory phenotype (SASP). These molecules account for the complex crosstalk between senescent cells and neighboring cells and the effect of cellular senescence in various physiological processes like aging and diseases like cancer.

Although senescence is regarded as a powerful barrier for tumor development, the SASP plays a role during tumor development promoting the growth of established tumors.

In a new study published in Nature Cell Biology, Zhang and colleagues pointed out a new mechanism that allows cells to turn on a set of genes encoding for the SASP molecules.

“This mechanism may potentially be targeted to stop the tumor-promoting aspect of senescence while preserving its antitumor function,” said Zhang.

The team focused on two proteins called METTL3 and METTL14 that are known for other molecular functions and found that these proteins moonlight as regulators of gene expression that help turn on SASP genes.

“Although we focused on senescence, we envision that this function of METTL3 and METTL14 may be involved in many other biological processes beyond our current study,” said Zhang. 

Low-dose Administration of MERS DNA Vaccine Candidate Induces Potent Immunity and Protects From Virus Challenge in Preclinical Models

PHILADELPHIA — (April 22, 2021) — A synthetic DNA vaccine candidate for Middle East respiratory syndrome coronavirus (MERS-CoV) developed at The Wistar Institute induced potent immune responses and afforded protective efficacy in non-human primate (NHP) models when given intradermally in abbreviated, low-dose immunization regimen. A similar vaccine candidate was previously shown to be safe and tolerable with a three-dose intramuscular injection regimen in a recently completed human phase 1 study and is currently in expanded studies of phase 1/2a trial. New results were published today in JCI Insight.

“While several vaccine products are being advanced against MERS and other coronaviruses, low-dose delivery and shortened regimes are crucial to rapidly induce protective immunity, particularly during emerging outbreaks, as the current SARS-CoV-2 pandemic has emphasized,” said David B. Weiner, Ph.D., Wistar executive vice president, director of the Vaccine & Immunotherapy Center (VIC) and W.W. Smith Charitable Trust Professor in Cancer Research, who led the study.

Researchers evaluated the immunogenicity and protective efficacy of their MERS synthetic vaccine when delivered intradermally using a shortened two-dose immunization schedule compared with intramuscular delivery of higher doses in NHP.

“Given that human efficacy trials for MERS vaccines may be challenging due to the low number of yearly cases, animal models such as our NHP model are valuable as a bridge with human data coming from early-phase clinical trials,” said Weiner.

In this study, Weiner and team report robust antibody neutralizing antibodies and cellular immune responses in all conditions tested. A rigorous virus challenge experiment showed that all vaccination groups were protected against MERS-CoV compared to unvaccinated control animals. However, the low-dose regimen with intradermal delivery was more impactful in controlling disease and symptoms than the higher dose delivered intramuscularly in NHP models.

“To our knowledge, this is the first demonstration of protection with an intradermally delivered coronavirus vaccine,” said Ami Patel, Ph.D., Caspar Wistar Fellow at the Vaccine & Immunotherapy Center and one of the lead authors of the paper. “Intradermal delivery of synthetic DNA vaccines has significant advantages for rapid clinical development. It can be dose sparing and has higher tolerability in people compared with intramuscular injection. The positive results of this study are important not only for the advancement of this MERS vaccine but also for development of other vaccines.”

“Our team is also advancing a COVID-19 vaccine through clinical trials, and we were able to do so in a very short time thanks to our previous experience developing the MERS vaccine,” added Weiner.

Importantly, no evidence of adverse effects on the lungs was observed in any of the dosing groups compared to unimmunized control animals. Through the assessment of a large panel of blood cytokines, researchers showed significant decrease in all mediators of inflammation, which further suggests the vaccine prevents the destructive inflammation induced by coronaviruses.

“In the past twenty years, three new coronaviruses have emerged and caused human outbreaks. The current SARS-CoV-2 pandemic has further emphasized the importance of rapid infection control for coronaviruses and other emerging infectious diseases,” said Emma L. Reuschel, Ph.D., a staff scientist in the Weiner lab and co-first author on the study. “Vaccine candidates that are simple to deliver, well tolerated, and can be readily deployed in resource-limited settings will be important to achieve control of infection.”

Co-authors: Ziyang Xu, Faraz I. Zaidi, Kevin Y. Kim, Regina Stoltz, and Kar Muthumani from The Wistar Institute; Dana P. Scott, Friederike Feldmann, Tina Thomas, Rebecca Rosenke, Dan Long, Jamie Lovaglio, Patrick W. Hanley, and Greg Saturday from National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT; Janess Mendoza, Stephanie Ramos, Laurent Humeau, and Kate E. Broderick from INOVIO Pharmaceuticals, Inc.

Work supported by: Funding from the Intramural Research Program, National Institutes of Allergy and Infectious Diseases, and the Coalition for Epidemic Preparedness Innovations (CEPI).

Publication information: Intradermal delivery of a synthetic DNA vaccine protects macaques from Middle East respiratory syndrome coronavirus, JCI Insight (2021). Online publication.


The Wistar Institute is an international leader in biomedical research with special expertise in cancer research and vaccine development. Founded in 1892 as the first independent nonprofit biomedical research institute in the United States, Wistar has held the prestigious Cancer Center designation from the National Cancer Institute since 1972. The Institute works actively to ensure that research advances move from the laboratory to the clinic as quickly as possible.

Women & Science: Developing Immunotherapies for Emerging Pathogens That Threaten Global Health

Wistar’s first Women & Science event of the COVID-19 era took place virtually and, appropriately, featured Dr. Ami Patel, a Wistar scientist that is playing a major role in the work being done at the Institute to develop solutions for the pandemic.

Dr. Ami Patel’s career path unfolded studying different emerging pathogens, each one scarier than the previous: from bird flu to the H1N1 swine flu to Ebola, and now SARS-CoV-2. This led her to work on developing next generation vaccine technologies as an alternative to traditional vaccine strategies that are not always effective against emerging infectious diseases.

Dr. Patel was recently appointed as a Caspar Wistar Fellow and is establishing her independent laboratory to develop next-generation immunotherapies and strategies for infectious diseases and cancer.

She believes the combination of different approaches being explored in this pandemic will be our winning strategy against COVID-19.

“The scientific community has really come together sharing information and resources, informing the public and letting science provide solutions. We are making a lot of advances in a short time,” she said.

Dr. Patel was instrumental in carrying out fundamental studies in animal models to understand what kind of immune responses are stimulated by the vaccine co-developed by Wistar and collaborators and inform what response would be observed in people during the clinical stage.

Wistar Appoints Ami Patel, Ph.D., as Caspar Wistar Fellow

PHILADELPHIA — (Sept. 14, 2020) — The Wistar Institute, an international biomedical research leader in cancer, immunology, infectious disease research, and vaccine creation, announces the appointment of Ami Patel, Ph.D., as a Caspar Wistar Fellow in the Vaccine and Immunotherapy Center.

Dr. Patel’s research focuses on strategies to combat emerging infectious diseases, including engineering vaccines and immunotherapies against viral and bacterial pathogens. Her independent program will expand Wistar’s expertise in pandemic preparedness and response to emerging outbreaks.

As a Caspar Wistar Fellow, Dr. Patel will embark on an independent path where her lab will harness the human immune system using next-generation technologies to improve public health.

“Emerging pathogens are of deep interest to me, as my work on the avian flu, swine flu, Ebola, and the current COVID-19 pandemic have demonstrated,” said Patel. “As an infectious disease scientist, I always ask myself ‘What will be the next outbreak, what do we need to understand to quicken our response and how can we help our bodies fight the pathogen?’ The COVID-19 pandemic is the perfect example of why reaction time to halt an outbreak matters and how effective technologies and resources are needed to develop vaccines. The Caspar Wistar Fellowship gives me the opportunity to pursue my own research ideas while still enjoying a lot of hands-on research and benefiting from mentoring in the highly collaborative environment at Wistar.”

The Caspar Wistar Fellows Program nurtures outstanding young scientists during their critical early years as independent investigators, creating a springboard for them to launch their careers and join the next generation of scientific leaders. The Program was made possible by the support of Wistar Board of Trustees member Doug Briggs and his wife Peggy.

“As a Wistar supporting partner, it is inspiring to see a promising early-career scientist that is so clear in her research goals and steadfast in her pursuit of biomedical innovation excellence,” said Doug Briggs. “Peggy and I could not be more pleased to see our second Caspar Wistar Fellow fast-tracked to reach her potential and beyond. We believe Dr. Patel will go on to do great things in science.”

Prior to her latest appointment, Patel conducted postdoctoral research at the San Raffaele Telethon Institute for Gene Therapy, Milan, Italy, and at Wistar in the lab of David Weiner, Ph.D. She received a Ph.D. in medical microbiology from the University of Manitoba, Winnipeg, Canada. Her doctoral research was performed in the Special Pathogens Program at the Public Health Agency of Canada, Winnipeg, Canada.

“Both mentorship and freedom to pursue a strong, independent research program are the key components to this Program,” said Dario Altieri, M.D., Wistar president and CEO. “I’m delighted that our quest to find the best and brightest led us to Dr. Ami Patel. Her research strengths in novel engineering approaches for in vivo gene delivery using DNA platforms for emerging infectious diseases and antimicrobial-resistant bacteria are a perfect asset as we build-out our pandemic response team.”


The Wistar Institute is an international leader in biomedical research with special expertise in cancer, immunology, infectious diseases and vaccine development. Founded in 1892 as the first independent nonprofit biomedical research institute in the United States, Wistar has held the prestigious Cancer Center designation from the National Cancer Institute since 1972. The Institute works actively to ensure that research advances move from the laboratory to the clinic as quickly as possible.

Spotlight on Wistar COVID-19 Researcher: Ami Patel, Ph.D.

Research assistant professor Ami Patel has spent her career committed to using novel engineering approaches to fight harmful infectious diseases. Her work focuses on developing next generation vaccines and immunotherapies using DNA as part of her toolset.  Dr. Patel has been at the forefront of the Wistar Vaccine and Immunotherapy Center’s response to the COVID-19 pandemic. She is a major scientific contributor to the preclinical studies that enabled one of the first vaccine candidates developed to rapidly move into clinical trials. Dr. Patel walks us through her work.

I have always been interested in infectious diseases and understanding how something that you can’t see with your eyes can make you sick. I am particularly fascinated about how infectious diseases are evolving and new infections are emerging for which existing drugs and vaccines are not effective. I am passionate about developing strategies to fine-tune our bodies to better fight these infections that affect global public health.

COVID-19 is the latest emerging pathogen, the so-called Disease X.  The scientific community is working hard to understand the biology of COVID-19; this information is vital for research teams like ours at Wistar so that we can develop drugs and vaccines to protect us all.

Historically, vaccine development is a very lengthy process. In this pandemic, the scientific community had to react rapidly to fast-track the work required to develop a vaccine. Research is developing at an astonishing speed and every day new studies come out that help us put together the very challenging puzzle that is COVID-19. Thanks to research advancements and new technologies, we have improved tools that make the design and initial testing of vaccines much faster than with traditional platforms.

Though we are under immense pressure to accelerate the path to human trials, rigorous preclinical testing remains an essential cornerstone in vaccine development, giving us a host of information on the vaccine candidate that will instruct clinical development. We are focusing our energy on developing the best possible vaccine candidate that we can and making sure that we test it rigorously in preclinical biomedical assays to support moving it to people.

My work, conducted at Wistar’s Vaccine & Immunotherapy Center led by Dr. David Weiner and in collaboration with our colleagues at Inovio Pharmaceuticals, was focused on just that: Making sure our novel synthetic DNA vaccine candidate is immunogenic in animal models and produces an immune response suitable for a potential vaccine candidate.

Preclinical testing of the new vaccine candidate was the basis for initiation of Phase 1 clinical trials that are currently being conducted in collaboration with researchers at the University of Pennsylvania. We recently published our findings in Nature Communications.

The immune response, as demonstrated by the antibodies produced by immunized animals, neutralized the virus, blocking its ability to interact with its receptor on host cells and preventing the virus from infecting them. The vaccine also activated specialized immune cell responses, known as T cells, which are also important for clearing infection from the body.

Yet, our work is not over. Our collaborators are conducting further testing in other larger animal models that are more similar to humans to give us an indication of the ability of the vaccine to effectively protect the body from getting infected.

In addition to vaccine work, which will hopefully help curb transmission and protect people from getting sick, we also need to advance better diagnostics and therapies to treat people that have become infected.

As many people are now aware, the most severe cases of COVID-19 are associated with lung inflammation. I am interested in applying what I have learned from the preclinical studies to design immune therapies that will reduce lung inflammation due to SARS-CoV-2 infection.

I am hopeful that we will get there with the joint effort of all scientists in the field. When I think about scientific progress, it is really about bringing global research together to conquer new frontiers and solve the most pressing problems that affect human health.

Positive Results from Preclinical Testing Support Clinical Development of COVID-19 DNA Vaccine

PHILADELPHIA — (May 20, 2020) — The Wistar Institute, an international biomedical research leader in cancer, immunology and infectious disease, announces a study reporting initial immunogenicity of a synthetic DNA vaccine for SARS-CoV-2 developed in collaboration with Inovio Pharmaceutical, Inc., and other scientists. Published in Nature Communications, the report focuses on immune studies in animals, which show induction of functional antibody responses and T-cell responses following immunization. The vaccine, INO-4800, was advanced to phase 1 clinical testing in 10 weeks ( NCT04336410).

The SARS-CoV-2 coronavirus emerged in December 2019 in the city of Wuhan, China. Infection causes the viral pneumonia disease COVID-19 that has spread quickly around the world. On March 11, 2020, the World Health Organization declared COVID-19 a global pandemic. Currently in the U.S., there are 1.5 million confirmed infections and more than 90,000 deaths occurring in just months, making COVID-19 infection the leading cause of death in the country.

No vaccines or major therapies are available to prevent infection or control the disease and the U.S. government has made development of a vaccine for COVID-19 a top priority. The viral genome became available on January 11, 2020, and the Wistar-Inovio team immediately began working to design and develop a new vaccine, based largely on their previous experience creating a synthetic DNA vaccine against the related coronavirus that causes Middle East respiratory syndrome (MERS).

Working with Inovio, a group led by David B. Weiner, Ph.D., Wistar executive vice president, director of the Vaccine & Immunotherapy Center (VIC) and W.W. Smith Charitable Trust Professor in Cancer Research, focused on rapid development of a synthetic DNA-based vaccine targeting the major surface antigen Spike protein (S) of SARS-CoV-2 into preclinical studies.

“We focused on both assay development and vaccination studies to test if immune responses induced by the vaccine in laboratory animals were functional against the virus. Our focus was the induction of immune responses that could in concept make it difficult for SARS-CoV-2 to have a home in the human body,” said Weiner, co-senior author of the publication. “The vaccine was designed leveraging our synthetic DNA technology, which has a set of conceptual advantages including accelerated clinical development built on a conceptually safe, non-live, simple platform that has scalable manufacturing and temperature stability. The vaccine-induced antibodies in vaccinated animals were of sufficient quantity and quality to block interaction of the virus with its receptor, which is its doorway into infecting the body, and were present in the lungs, a place where immunity is very important. The vaccine also induced T-cell function, which is critical for clearing viral infections from the body. These are indications that the immunity it induced might provide no escape for the SARS-CoV-2 virus. We are looking forward to additional studies and examining data from the ongoing clinical trial.”

The team includes Wistar VIC investigators Daniel Kulp, Ph.D., Kar Muthumani, Ph.D., and Ami Patel, Ph.D., who is a shared first author in the paper.

DNA vaccines work by delivering the genetic information required to make a certain viral protein in the recipient’s body, which stimulates the immune system to recognize that protein as foreign and build a response against it, thus targeting the virus and providing protection from infection.

Expressed in vitro, INO-4800 induced robust expression of the S protein. Within days following a single immunization of mice and guinea pigs, the vaccine induced antigen-specific T cell responses and functional antibodies that neutralize the virus, blocking the ability of the SARS-CoV-2 S protein to bind to the angiotensin-converting enzyme 2 (ACE2) host receptor on human cells.

Importantly, SARS-CoV-2-specific antibodies were detected in the lungs of immunized animals, suggesting they might protect against upper and lower respiratory disease that is associated with severe cases of COVID-19.

“While this candidate continues its journey as a potential vaccine against COVID-19, we are continuing our work in the lab to gather more information on the vaccine’s performance in small and larger animals,” said Patel, who is a research assistant professor at Wistar. “We will further characterize antibody functionality, cellular responses, and the ability of INO-4800 to mediate protection of animals against viral challenge.”

Co-authors: Trevor R.F. Smith and Stephanie Ramos from Inovio co-first authors. Other co-authors include Xizhou Zhu, Ebony N. Gary, Susanne N. Walker, Mansi Purwar, Ziyang Xu, Pratik Bhojnagarwala, Neethu Chokkalingam, Elizabeth Parzych, Emma L. Reuschel, Nicholas Tursi, Jihae Choi, Edgar Tello-Ruiz, Mamadou A. Bah, Yuanhan Wu, Daniel Park, Yaya Dia, Ali Raza Ali, Faraz I. Zaidi, Kevin Y. Kim, Sophia Reeder, Makan Khoshnejad, Jacqueline Chu, Kar Muthumani, and Daniel W. Kulp from Wistar; Dustin Elwood, Jian Yan, Katherine Schultheis, Jewell Walters, Maria Yang, Patrick Pezzoli, Arthur Doan, Miguel Vasquez, Igor Maricic, Dinah Amante, Alison Generotti, Timothy A. Herring, Ami Shah Brown, J Joseph Kim, Jean Boyer, Laurent M.P.F. Humeau, and Kate E. Broderick (corresponding author) from Inovio Pharmaceuticals; Nianshuang Wang, Daniel Wrapp, and Jason S McLellan from University of Texas at Austin; and B Wang from Fudan University, China.

Work supported by: Funding from the Coalition for Epidemic Preparedness Innovations (CEPI).

Publication information: Immunogenicity of a DNA vaccine candidate for COVID-19, Nature Communications (2020). Online publication.


The Wistar Institute is an international leader in biomedical research with special expertise in cancer research and vaccine development. Founded in 1892 as the first independent nonprofit biomedical research institute in the United States, Wistar has held the prestigious Cancer Center designation from the National Cancer Institute since 1972. The Institute works actively to ensure that research advances move from the laboratory to the clinic as quickly as possible.

Moving the Needle Forward: Wistar Research Leads to a Coronavirus Vaccine Entering Human Trials and Additional Wistar Coronavirus Research Projects Underway

While the world struggles with a growing number of people sickened with COVID-19 and health care workers engage in a tireless and heroic mission to save lives, biomedical researchers are on the front lines of a parallel and equally critical battle to develop new tools to effectively diagnose, treat and prevent a disease we are still learning about.

Scientists at The Wistar Institute’s Vaccine & Immunotherapy Center (VIC) have been working long hours and over weekends, devising new strategies to apply their expertise and technological platforms to combat SARS-Cov-2. 

So far, the work has paid off. The second COVID-19 vaccine to move into clinical testing in the U.S. is due in part to Wistar’s effort and comes from the team led by Dr. David Weiner and including Drs. Daniel Kulp, Ami Patel and Kar Muthumani, in collaboration with biotech company Inovio Pharmaceuticals, Inc.

This vaccine, based on synthetic DNA technology, was advanced in record time from computer design to preclinical testing in just under three months. Results from preclinical studies show the vaccine is effective at inducing both antibody and T cell-mediated responses soon after delivery in mice and guinea pigs, allowing researchers to unlock the next step — human testing subsequent to FDA approval.

Data from these studies are available to the scientific community while the manuscript is under consideration for publication in a high-impact journal.

Even though the vaccine will go through further testing in the lab as new tools and reagents become available, scientists have passed the baton to their pharmaceutical partner and the doctors and clinical experts working with the company to evaluate the safety of the coronavirus vaccine in people.

Announced by Inovio on Monday, April 6, the vaccine just entered a phase 1 clinical study coordinated by the University of Pennsylvania. 40 healthy adult participants in Philadelphia and Kansas City, Missouri will receive two vaccine doses four weeks apart, and initial data on immune responses and safety from this study are expected by late summer.

“I am extremely proud of all the work done by our scientists for this vaccine and the role played by Wistar as an academic engine of new technologies that are the basis for future medicines,” said Dario C. Altieri, M.D., Wistar president and CEO. “Hopefully, one day not so long from now, we will have a preventative vaccine to help curb the pandemic. It would be another enormous Wistar contribution to human health.”

In these times we need as many tools as possible to stem the pandemic. Wistar scientists are actively developing other vaccine approaches and therapeutic strategies, ranging from tricking the virus into attaching to decoy receptors to prevent it from infecting cells, to reducing inflammation that causes disease severity in those infected with the virus, to alternative ways to make and deliver protective antibodies that will neutralize the virus.

Although in early stages, most of this research has the potential to be advanced fairly quickly due to the nature of the approaches and our scientists’ previous experience with tackling other infectious agents.

“We are very excited about the potential of our COVID-19 vaccine,” said Weiner. “The preclinical results thus far motivate us to focus our efforts in additional directions and do our best to advance more approaches that can ultimately make a difference in this pandemic.”

To catalyze Wistar’s coronavirus research endeavor, the Institute recently launched the Wistar Coronavirus Discovery Fund, which will support a range of research programs and enhance the ability of our scientists to pursue innovative solutions as quickly as possible.

As the World Health Organization remarked, “Coronavirus research has accelerated at incredible speed…” because scientists, funders and international organizations have come together to solve the crisis. 

“We are all in this together and together we can all do our part,” said Weiner. 

Wistar Translational Research in Response to the COVID-19 Pandemic

The Wistar Institute’s Vaccine & Immunotherapy Center (VIC) has assembled its expertise in infectious disease research, as its scientists are part of a team racing to provide a countermeasure for the ongoing coronavirus outbreak. 

A historic leader with a track record of successful vaccines that have saved millions of lives, Wistar is now leveraging synthetic DNA technology to develop a vaccine against the coronavirus. 

The laboratory of Dr. David Weiner, Wistar executive vice president, director of the VIC and the W.W. Smith Charitable Trust Professor in Cancer Research, has worked for several decades advancing the technology for generating synthetic DNA vaccines that can be used for global pandemic outbreaks. 

In December 2019, Drs. Weiner, Ami Patel, Kar Muthumani, and Dan Kulp at Wistar along with colleagues at Inovio Pharmaceuticals, Inc., Drs. Joseph Kim, Laurent Humeau and Kate Broderick, were paying particular attention to the new outbreak in Wuhan, China, caused by a virus identified as a novel coronavirus. Infections were rapidly expanding in China, and by mid-January they were starting to spill over to other countries. COVID-19, as the infection was eventually named, was not going away. The team decided to work together tackling the outbreak as soon as the opportunity to jump in arose, as they have collaborated to advance vaccines for other outbreak pathogens. 

Synthetic DNA would not need the virus itself to build vaccine candidates, as these can be modeled and developed through computer analysis of the viral sequence, using predictions based on prior experience to synthesize a prototype DNA vaccine for rapid testing. The team would use their extensive MERS coronavirus vaccine experience as a model, taking into account unique features displayed by the new coronavirus in the design. In January, as the cases increased, a consortium led by Dr. Yong-Zhen Zhang of the Shanghai Public Health Clinical Center & School of Public Health posted the first viral DNA sequences online. 

“This provided the opportunity the team was waiting for,” said Dr. Weiner. Within hours, prototype vaccines were designed and moved to development.  

The designed DNA vaccine encodes a tailored sequence as the code for the vaccine. When the vaccine is administered to a recipient, the genetic sequences are then delivered inside the cells and instruct the cells to assemble a new protein shaped like a piece of the virus. Similar to using Lego blocks, a 3-D replica of a viral antigen is built inside the body and teaches the immune system what to look out for and destroy — reproducing what would happen if the person came in contact with the true virus. 

Coronaviruses are large RNA viruses that get their name from the ‘halo’ generated by the spike protein that decorates the surface of these viruses. When a coronavirus is viewed in the laboratory using electron microscopy, the spike proteins appear to form a crown. The new strain of coronavirus has been designated SARS-CoV-2 and is the entity that causes the COVID-19 disease. 

SARS-CoV-2 is an emerging pathogen that human populations have not previously experienced although it belongs to the same family as the coronaviruses that caused Severe Acute Respiratory Syndrome (SARS), an outbreak originating in China that the world experienced in the early 2000s, and Middle East Respiratory Syndrome (MERS), an outbreak originating about a decade later in the Middle East that, while controlled, still smolders. 

The team has significant experience in developing countermeasures for a coronavirus outbreak. A synthetic DNA MERS vaccine they developed advanced into phase 2 clinical study, having achieved relevant vaccine milestones including protection of laboratory animals from infection, human safety, and immunogenicity. 

The new coronavirus vaccine effort by the Weiner team is one of a handful supported by the Coalition for Epidemic Preparedness Innovations (CEPI) for the rapid development of new vaccine approaches to the coronavirus outbreak. CEPI is a global alliance led by Norway along with several other countries with major funding from philanthropic organizations. Assembled just more than three years ago to fast-track translational vaccine approaches for emerging pandemics, the organization has been comparing vaccine technologies that could be utilized rapidly in an outbreak situation with the foresight of stemming worldwide epidemics using scientific innovations through new technology. 

That preparation is being put to the test in support of developing a vaccine response for COVID-19. In January, CEPI started to discuss funding a program for clinical vaccine development with the team. On January 23, at the World Economic Forum in Davos, CEPI announced its support for three teams based on their technologies and accomplishments showing their vaccines can be rapidly created, tested, generate consistent immunity, and can be advanced in a conceptually safe fashion to clinical trials.  

Each team funded by CEPI is comprised of industry partners and academic vaccine teams that work together to move the novel candidates through early development and into clinical study and then, if applicable, advance them to efficacy trials. This approach combines the research speed of academic investigators with the focused development and clinical production and regulatory strengths of industry leaders who are at the forefront of their technologies. 

The Initial teams were: 

  • GlaxoSmithKline (GSK) in partnership with the University of Queensland, Australia, for a recombinant protein and adjuvant approach. 
  • Moderna Therapeutics, Inc., in partnership with the National Institute of Allergy and Infectious Diseases (NIAID) Vaccine Research Center for a mRNA approach; and 
  • Inovio in partnership with The Wistar Institute’s VIC team. 

Five additional teams have recently been added by CEPI.

“It’s a very unique situation — it’s the first time we’re seeing a global vaccine coordinated response like this, thanks to the speed with which CEPI acted and funded the initial teams,” said Weiner. “We are honored to be able to contribute to this important effort under the advanced DNA vaccine technology program of Inovio for COVID-19.”  

The team reported immune responses to the new synthetic DNA vaccine that were induced in several animal model species after a single immunization — the first program to do so.  

CEPI’s stated initial goal was to speed advancement of the new coronavirus vaccines to phase 1 trials in four months or less. The CEPI program has made a significant difference already in mobilizing the vaccine community to advance products for COVID-19. This week, Moderna announced that they have opened their phase 1 clinical trial. Inovio announced that a phase 1 study of the synthetic DNA vaccine is preparing to open in April.  

As of March 23, just 3.5 months into this outbreak, there are approximately 372,000 reported infections with more than 16,300 deaths spread over 168 countries. In the U.S., there are over 41,000 cases which have resulted in 573 fatalities. New York has more than 12,000 cases*.  

“The Wistar Institute’s VIC works to provide new immune approaches and understanding to impact important human disease. We need countermeasures for the COVID-19 pandemic,” said Weiner. “All of us are in this together and the more tools in the toolbox, the better equipped we are to possibly protect our vulnerable populations and our first-line defenders. Rapidly advancing these tools is only the first step in this process, but it’s an important one.”

* Source: Center for Systems Science and Engineering at Johns Hopkins University