News

WXXI hosts a live, televised forum addressing COVID-19 vaccines.

Local experts on the latest COVID-19 vaccine research gathered for a live forum on WXXI-TV and radio Thursday night. Those on the panel said they see reason for hope, but they also caution it will take some time for the community to build up immunity to the virus.

Researchers on the program from the University of Rochester Medical Center included Dr. Angela Branche, co--director of the URMC Vaccine Trials and Evaluation Unit. Branche talked about the challenge to get past the mistrust that some people in the Black community have regarding medical research, when the vaccine becomes more widely available.

"And we're really going to have to work with our community partners, leaders and activists in the community who already have established trust with these groups that we're talking about and partnering with them and giving them educational tools and helping them deliver the message is really what's going to be the most effective," Branche said.

Monroe County's commissioner of Public Health, Dr. Michael Mendoza also sees a need to provide as much outreach and education to the community as possible about the vaccine. And he emphasized the need to continue following guidelines about wearing masks and physical distancing, because it will take a while to get most people inoculated.

"We have a vaccine on the ground, there are people who are getting the vaccine now, but the reality is that there is still so much time between now and when this is over."

Mendoza said that right now he is concerned about the rapidly increasing numbers of people being hospitalized and how that could impact health care in general in the Finger Lakes region.

Minsoo Kim, Ph.D was recognized recently with the Davey Award, an honor bestowed on University of Rochester/Wilmot Cancer Institute faculty members who have made outstanding contributions to cancer research.

The University of Rochester Medical Center (URMC) has created a new institute that will strengthen and accelerate the study of viral, bacterial, and fungal pathogens. The Translational Immunology and Infectious Diseases Institute (TIIDI) will build upon decades of scientific research leadership in the human immune system, respiratory viruses, and vaccine development, and, more recently, the Medical Center's role in the national response to the coronavirus pandemic.

The new Institute -- which is led by David J. Topham, Ph.D., and was approved by the University of Rochester Board of Trustees last month -- will bring together multi-disciplinary teams of scientists and clinicians that will take the knowledge gained from basic research in immunology, microbiology, and virology and apply it to problems in human diseases caused by infectious pathogens. TIIDI will also strengthen education and training programs to build a pipeline that produces the next generation of adult and pediatric clinician-researchers in the field.

Researchers will study infectious diseases across several areas of medicine, including immunodeficiency, cancer, transplant, orthopedics, ophthalmology, dermatology, gastroenterology, autoimmunity, neonatology, and public health. TIIDI will focus on the development of new treatments and vaccines, and strategies to better control the spread of infectious diseases, such as HIV, respiratory pathogens, and hospital acquired infections. Researchers will also study the pathology of infectious diseases to better assess risk factors for severe outcomes and develop more effective early interventions.

What are you and your institution currently working on regarding COVID-19?

The Topham Lab launched a coronavirus research study to understand how the immune system responds to acute COVID-19 infection, including how long immunity lasts once a person has been infected and recovered. We have evidence of pre-existing cross-reactive memory B cells and Original Antigenic Sin in infected subjects. We are also collaborating with researchers at New York University and University of Idaho to examine whether mothers can transmit COVID-19 through breast milk (they don't) and whether the breast milk itself has immunological properties against the disease (it does). Funded by the Bill and Melinda Gates Foundation and the NIH, the study could result in critical guidance for current and soon-to-be mothers. Physicians at URMC and Rochester Regional Health are investigating a new coronavirus vaccine developed by Pfizer and BioNTech. The URMC Vaccines and Treatments Evaluation Unit is testing Remdesivir combined with other drugs, as well as a Phase III clinical trial of the Astra Zeneca ChAdOX-1 SARS-CoV-2 vaccine. Rochester engineers and medical scientists are collaborating closely with clinicians to develop tests to detect coronavirus. Projects include (1) research on a finger-stick test to detect and study immunity to COVID-19; (2) the creation of tiny sensor chips that use coronavirus proteins to "very quickly" detect the presence of antibodies that help humans fight against the virus; and (3) testing samples of sputum, nasal mucus, or blood using ultrathin silicon nanomembranes to "instantly" determine if an individual has been infected. The Lung Development Molecular Atlas Program (LungMAP) and the Human BioMolecular Atlas Program (HuBMAP) collaboratives received funding from the NIH to examine human lung tissue in order to determine why children seemingly contract COVID-19 at a lower rate and remain more asymptomatic than the older population. Gloria Pryhuber, professor of Neonatology, will lead URMC's involvement in this multi-institutional project. The New York State Emerging Infections Program (EIP) is part of the federal Centers for Disease Control & Prevention's national effort to provide population-based communicable disease data to identify disease patterns, to evaluate vaccine programs, and to identify at-risk populations. The URMC EIP will be performing laboratory and population-based surveillance for COVID-19 as a part of multi-site national study. The group will collect a variety of demographic and clinical data that will be reported to the Centers for Disease Control & Prevention and the Monroe County Department of Public Health.

Please describe your research involving antibodies, memory B-Cells and the S-Subunit?

Dr. Mark Sangster in the Topham Lab has been studying acute and memory B cell (MBC) responses to COVID-19. We found evidence of pre-existing cross-reactive MBC specific for the S2 subunit of the spike glycoprotein and seasonal beta coronaviruses. This cross-reactive MBC responds more rapidly to infection and may affect responses to other SARS-CoV-2 proteins. Antibodies to the S2 subunit can be neutralizing. We are now trying to understand whether this immune memory is correlated with disease outcomes. We are also beginning studies of T cell responses to SARS-CoV-2 in acute and convalescent subjects.

Professional Summary

David Topham joined the faculty at the University of Rochester Medical Center in 1999 and was appointed in 2009 as Vice Provost and Executive Director of the Health Science Center for Computational Innovation (HSCCI), a partnership between New York State, the University and IBM. As Executive Director of the HSCCI, Dr. Topham's responsibility is to support collaboration in biomedical research using High Performance Computational Resources. He will bring together academic biomedical and health-related Research Investigators, High Performance Computational Biologists, and HP Research Computing resources. Dr. Topham provides strategic direction to the HSCCI and facilitates the development of research projects between UR scientists and its corporate partners, as well as support from state and federal agencies.

Dr. Topham is a Professor of Microbiology and Immunology, a member of the David H. Smith Center for Vaccine Biology and Immunology, and directs the New York Influenza Center of Excellence--one of the five national Centers of Excellence in Influenza Research and Surveillance supported by the NIH.

Dr. Topham was recently appointed as the Founding Director of the UR Translational Immunology and Infectious Diseases Institute whose mission is to foster collaborative team based approaches to translational research on infectious diseases and immunology.

About Topham Lab

Viruses that infect the respiratory tract are responsible for extensive morbidity and mortality in human population worldwide. Influenza virus is a particular concern because of its ability to periodically cause deadly pandemics, most recently in 2009 after the spread of a swine-origin H1N1 virus to humans. Novel avian influenza viruses such as H5N1 and H7N9 continue to cause sporadic cases of severe disease in humans and are an ongoing pandemic threat. An understanding of how the immune system controls influenza and other respiratory viruses and provides long-term protection is critical for the rational development of effective vaccination and treatment strategies.

Studies in our lab are primarily aimed at understanding the multiple roles of virus-specific B and T cells in determining the outcome of viral infection of the respiratory tract. In particular, we are interested in the character, longevity, and protective capacity of B and T cell memory induced by infection and vaccination. A large component of work in the lab focuses on the response of the human immune system to infection and vaccination; other work uses a variety of animal model systems to investigate basic immunological mechanisms. A recent initiative in the lab is the identification of viral genes and host responses that influence the severity of respiratory virus infections. This work will identify strategies for engineering new antivirals and improving vaccines.

Many projects involve strong collaborative interactions within centers at the University of Rochester that focus on immunity to respiratory pathogens. These centers include the Respiratory Pathogens Research Center (RPRC), the New York Influenza Center of Excellence (NYICE), and the University of Rochester Genomics Research Center (URGRC).

Felix Yarovinsky has been appointed as a Chair of the Innate Immunity and Inflammation (III) Study Section, NIH.

Congratulations!

Seasonal colds are by all accounts no fun, but new research suggests the colds you've had in the past may provide some protection from COVID-19. The study, authored by infectious disease experts at the University of Rochester Medical Center, also suggests that immunity to COVID-19 is likely to last a long time -- maybe even a lifetime.

The study, published in mBio, is the first to show that the COVID-19-causing virus, SARS-CoV-2, induces memory B cells, long-lived immune cells that detect pathogens, create antibodies to destroy them and remember them for the future. The next time that pathogen tries to enter the body, those memory B cells can hop into action even faster to clear the infection before it starts.

Because memory B cells can survive for decades, they could protect COVID-19 survivors from subsequent infections for a long time, but further research will have to bear that out.

The study is also the first to report cross-reactivity of memory B cells -- meaning B cells that once attacked cold-causing coronaviruses appeared to also recognize SARS-CoV-2. Study authors believe this could mean that anyone who has been infected by a common coronavirus -- which is nearly everyone -- may have some degree of pre-existing immunity to COVID-19.

"When we looked at blood samples from people who were recovering from COVID-19, it looked like many of them had a pre-existing pool of memory B cells that could recognize SARS-CoV-2 and rapidly produce antibodies that could attack it," said lead study author Mark Sangster, Ph.D., a research professor of Microbiology and Immunology at URMC.

Sangster's findings are based on a comparison of blood samples from 26 people who were recovering from mild to moderate COVID-19 and 21 healthy donors whose samples were collected six to 10 years ago -- long before they could have been exposed to COVID-19. From those samples, study authors measured levels of memory B cells and antibodies that target specific parts of the Spike protein, which exists in all coronaviruses and is crucial for helping the viruses infect cells.

Whether flu or coronavirus, it can take several days for the body to ramp up an effective response to a viral infection. New research appearing in the journal Nature Immunology describes how different cells in the immune system work together, communicate, and -- in the case of cells called neutrophils -- bring about their own death to help fight off infections. The findings could have important implications for the development of vaccines and anti-viral therapies.

"The immune system consists of several different types of cells, all acting in coordination," said Minsoo Kim, Ph.D., a professor of Microbiology and Immunology at the University of Rochester Medical Center (URMC) and senior author of the study. "These findings show that cells called neutrophils play an important altruistic role that benefits other immune cells by providing key resources for their survival and, in the process, enhancing the body's immune response against a virus."

Neutrophils are a key component of the innate immune system, the part of the body's defenses that is always switched on and alert for bacterial and viral invaders. The vast majority of white cells circulating in blood are neutrophils and, as a result, these cells are the first on the scene to respond to an infection.

However, neutrophils are not fully equipped to eliminate a viral threat by themselves. Instead, when the respiratory tract is infected with a virus like influenza or COVID-19, a large number of neutrophils rush to the infection site and release chemical signals. This triggers the production of specialized T cells, which are part of the body's adaptive immune system, which is activated to produce a more direct response to specific infections. Once mobilized in sufficient quantities, a process that typically takes several days, these T cells target and ultimately destroy the infected cells.

The new study, which was conducted in mice infected with the flu virus, shows that in addition to jump-starting the adaptive immune response, neutrophils have one more important mission that requires that they sacrifice themselves. As T cells arrive at the infection site, the neutrophils initiate a process called apoptosis, or controlled death, which releases large quantities of a molecule called epidermal growth factor (EGF). EGF provides T cells with the extra boost in energy necessary to finish the job.

"This study represents an important paradigm shift and shows that the adaptive immune system doesn't generate a successful response without instruction and help from the innate immune system," said Kim. "The findings reveal, for the first time, how different immune cells work together, and even sacrifice themselves, to accomplish the same goal of protecting the host from the viral infection."

The P01 focuses on the cellular dynamics of inflammatory disease and the regulation of immune function. The goal of this pilot program is to develop new collaborations with researchers developing novel imaging techniques, computational image processing and data analysis, single cell and spatial transcriptomics, optogenetics and new mouse models of infections or immune mediated disease. Successful projects will have a collaborative component with one of the existing P01 faculty (Drs. Deborah Fowell, Minsoo Kim, David Topham, Jim Miller, Patrick Oakes, Nozomi Nishimura). Applicants are encouraged to contact P01 faculty members to discuss their potential project before submission.

Applicants may request a maximum of $40,000 Direct Costs for the duration of one year and must hold a faculty level position. Funds are restricted to research expenses and staff salaries, and cannot be used to support travel, faculty salary, or equipment purchases.

Initial applications should include a one-page abstract describing the goals and objectives of the proposed project, the relevance to the mission of the P01, and the investigators involved (there is no form template for the abstract portion). It is critical that research ideas are expressed in such a way that a non-expert can understand the ideas and appreciate their significance and potential impact. Additionally, funds may only be spent between January 1, 2021 and December 31, 2021, so awardees must commit to completing the specific aims of the project within the allowed one-year time period. Abstracts will be reviewed and those applicants selected to submit full applications will be contacted shortly thereafter.

The deadline for submitting initial applications is October 30, 2020

Questions? Contact Deborah Fowell, Minsoo Kim, or Stefanie Fingler or visit the Program for Advanced Immune Bioimaging web site.

Please submit your abstracts to Stefanie Fingler via email to the address above.

With millions of lives on the line, researchers have been working at an unprecedented pace to develop a COVID-19 vaccine.

But that speed—and some widely touted breakthroughs—belie the enormous complexity and potential risks involved. Researchers have an incomplete understanding of the coronavirus and are using technology that's largely unproven.

Among many worries: A handful of studies on COVID-19 survivors suggest that antibodies—key immune system proteins that fight infection—begin to disappear within months. That's led scientists to worry that the protection provided by vaccines could fade quickly as well. Some even question whether vaccines will really end the pandemic. If vaccines produce limited protection against infection, experts note, people will need to continue wearing masks and social distancing even after vaccines roll out.

People with severe symptoms from COVID-19 tend to have higher antibody levels than those with milder cases.

Some people fail to generate antibodies because they have compromised immune systems, said Mark Sangster, a research professor at the University of Rochester Medical Center.

Even when people do generate antibodies against the novel coronavirus, studies suggest the antibodies may not last long.

NIAID is funding a CEIRS network wide COVID-19 and influenza Southern Hemisphere surveillance study, "Natural history of SARS-CoV-2 in comparison to influenza A virus: a multi-site study focused in the Southern Hemisphere and equatorial regions."

The New York Influenza Center of Excellence, at the University of Rochester, under the direction of Dr. David Topham, will receive just over $1M in funding. Dr. Topham's lab has partnered with investigators in Australia and Vietnam to carry out the proposed research, which will include samples from Vietnam that will be shipped to Rochester for immune response analysis. The Australian samples will be analyzed at the WHO collaborating center for influenza located at the Doherty Institute in Melbourne.

Together, the CEIRS Network offers a unified human surveillance effort designed to gather critical information on the spectrum of disease, risk factors, duration of viral shedding, viral genomics, viral dynamics within and between populations and innate and memory immune responses to infection. By targeting international locations where seasonality is muted or winter is just beginning, we will gain much-needed insight into the impact of the seasons on SARS-CoV-2 spread. We will furthermore capture co-circulation of SARS-CoV-2 with other respiratory viruses, including influenza viruses, allowing a valuable comparative approach to be taken in our clinical, virological and immunological analyses.

We congratulate Dr. Deborah Fowell on her new position as Chair of the Department of Microbiology and Immunology at Cornell University College of Veterinary Medicine, where she will start this fall. As a valued faculty member and Dean's Professor in the Department of Microbiology and Immunology, Center for Vaccine Biology and Immunology, this is a bittersweet goodbye -- but a wonderful new opportunity for Deb!

Since joining UR in April 2000, Dr. Fowell has achieved great success in her research program. One example is her organization and leadership of an accomplished, interdisciplinary team of investigators in an NIH funded program project to visualize the immune system in action, which was recently renewed. Her efforts have led to tremendous advancements in the field and will continue to enhance our understanding of tissue inflammation and immune responses, while also providing new therapeutic targets for mitigation of a wide variety of inflammatory diseases.

Not only is Dr. Fowell an outstanding researcher, she is also deeply committed to excellence in graduate education. She recently took over as Program Director and successfully renewed the University's Predoctoral Training Grant in Immunology. In addition, she has received multiple mentoring awards at the UR, including the 2015 Graduate Alumni Award, which is the most prestigious student teaching and mentoring award here at the School of Medicine and Dentistry.

Dr. Fowell has a strong reputation among her peers as a highly innovative researcher with rigorous intellectual standards, and as a consistent advocate of the highest quality science and long-term success for academic research. Her collaborative approach to research, commitment to enriching learning and intellectual discourse, coupled with her drive and energy, will ensure her success at Cornell.

It's with pride, warm wishes and anticipation of exciting future collaborations that we wish Deb every success in her new role!

The University of Rochester Medical Center (URMC) have launched a new study to understand how the body's immune system responds to COVID-19, including if and when a person could be re-infected with the virus and whether some people have pre-existing immunity. The findings could have significant implications for the public health response to the pandemic, the development of COVID-19 vaccines, and decisions related to re-opening the economy and society.

This study was featured on 13WHAM.

The new coronavirus research is being led by David Topham, Ph.D., Angela Branche, M.D., and Ann Falsey, M.D., under the URMC New York Influenza Center of Excellence(NYICE), one of the five international centers in the Centers of Excellence in Influenza Research and Surveillance network. The research is supported by approximately $5 million in funding from the National Institute of Allergy and Infectious Diseases (NIAID), the institute headed by Anthony Fauci, M.D.

"This research will seek to answer several important questions, including the durability of immunity from the virus once a person has been infected and recovered, whether the virus is mutating, whether previous exposure to other seasonal coronaviruses provides a degree of protection from COVID-19, and how long potential vaccines could provide immunity from the virus," said Topham.

The study will recruit up to 100 COVID-19 positive individuals across all age groups from the Rochester community and follow them for 90 days. The researchers will collect samples that will enable them to isolate and study the virus, and measure immune response to the infection.

Specifically, it will track the production of antibodies that seek out and flag the virus for destruction by immune cells. Once produced in sufficient quantity, these antibodies and other cells generated by the immune system provide protection from re-infection. These cells are also activated after vaccination. However, as is the case with other viral infections such as the flu, it is speculated that immunity to COVID-19 will weaken over time.

This research builds on more than a decade of influenza and respiratory pathogens research by the NYICE. For the past 13 years, URMC researchers have been conducting surveillance studies in an effort to better understand the immune response to the flu and vaccination. At the request of NIAID, URMC researchers have retooled and expanded the influenza study to include on COVID-19.

Dr. Topham was featured in the Rochester Beacon today in the Health & Science section.

Good news is that an antiviral treatment effective against the new coronavirus could start to be available in as little as three months and could be tested on some local coronavirus patients even sooner. The bad news is that every other warning and caution against the potentially deadly virus still applies and will continue to apply for the foreseeable future.

There is more good news though. The antiviral is remdesivir, a drug that has previously been used to help combat Middle East Respiratory Syndrome, also known as MERS, and Severe Acute Respiratory Syndrome, or SARS viral infections and is thus already produced, with some stockpiles available, and known to be safe.

The three-month timeline for remdesivir's availability as an anti-corona virus agent is the informed projection of David Topham, a University of Rochester Medical Center virologist and immunologist whose local laboratory is one of five in New York State involved in researching COVID-19, the new coronavirus rapidly spreading to pandemic proportions. His lab is tied into a national and global network of researchers studying the disease.

Farewell for Americo Lopez Yglesias, a very successful trainee #12 moving to his faculty position at the University of Indiana!