Tag: Patel

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.”

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. 

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