News

Francisco Chaves

The Topham and Sant laboratories in the David H. Smith Center for Vaccine Biology & Immunology would like to acknowledge the 15 years of outstanding technical support and immunology research provided by Mr. Francisco Chaves. Francisco joined the University in 2002 as part of the Sant lab, which had just moved here from the University of Chicago. Almost 3 years ago, Francisco joined the Topham Lab where he is currently employed. Francisco has many research skills and talent, but he is perhaps best known for his prowess with protein biochemistry. He has had a long standing interest in the biochemistry of peptide:MHC class II complexes, responsible for activation of CD4 T cells, and published many seminal studies on his work in the Sant laboratory. These studies are critical in understanding the factors that dictate CD4 T cell immunodominance hierarchies and have formed the basis of ongoing efforts in rational vaccine design.

One of his current projects is the cloning, engineering, and production of recombinant influenza hemagglutinin (HA) proteins for use as antigens and as probes for identifying HA specific B cells in the peripheral blood of people either infected with influenza or recently vaccinated. One of the goals of this project is to better understand how B cell memory contributes to, or influences, subsequent encounters with new HA antigens in circulating viruses or updated seasonal vaccines. He has also produced H7 HA probes for studies that are part of a clinical trial of experimental H7N9 avian influenza vaccines.
Congratulations Francisco!

New publication "Natural and directed antigenic drift of the H1 influenza virus hemagglutinin stalk domain," discusses universal strategy against influenza virus infections. Full text available.

Study shows pros, cons for major strategy to create broadly protective shot

David J. Topham, Ph.D.

Flu shot season is here. But as you head to the doctor's office or pharmacy to get vaccinated, scientists are working to make this yearly ritual a thing of the past. Researchers around the world, including at the University of Rochester Medical Center (URMC), are pursuing a "universal" flu vaccine, one that would protect against most or all seasonal and pandemic strains of the flu virus.

This is no easy task, and a study out today in the journal Scientific Reports suggests that one of the most promising strategies -- creating a vaccine that targets the "stalk" of a protein that covers the flu virus -- is a strong one, but isn't completely bulletproof.

The hemagglutinin protein, which blankets the outside of the flu virus, looks a bit like a flower; it has a stalk (think stem) and a head (think petals). Current vaccines target the head, which is the part of the virus that's always changing in an effort to evade our immune defenses. The head sits on the stalk, and it's believed that the stalk stays relatively constant from one strain of flu to another. Directing a vaccine and the body's immune response towards the stalk is a seemingly logical strategy for creating a shot that would provide broad protection.

But, contrary to current assumptions, researchers at the URMC-based New York Influenza Center of Excellence (NYICE) found that the stalk can change, although not as easily or frequently as the head.

Using supercomputers at the University's Health Sciences Center for Computational Innovation, they analyzed the genetic sequences of human H1N1 flu viruses circulating since 1918. They found variations in both the head and the stalk, although variability was highest in the head region.

NIH-Led meeting identifies knowledge gaps, development goals

Colorized transmission electron micrograph showing H1N1 influenza virus particles. NIAID

What

Scientists and clinicians from the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, and the California Institute of Technology discuss key considerations for developing a universal influenza vaccine in a meeting report appearing in the October 17 issue of Immunity. The report summarizes discussions from a workshop NIAID held June 28-29, 2017, in Rockville, Maryland, entitled, “Pathway to a Universal Influenza Vaccine.” The workshop brought together U.S. and international experts from academia, industry and government to identify knowledge gaps in influenza research and to set goals to fill these knowledge gaps. NIAID will use the report to develop a strategic plan and research agenda aimed at the development of a universal influenza vaccine.

Licensed influenza vaccines provide suboptimal protection against seasonal influenza, must be updated regularly to match circulating influenza strains, and offer little or no protection against newly emerged pandemic influenza strains. Thus, a key public health goal is to develop a universal influenza vaccine that would protect against most or all seasonal strains of influenza virus and potential pandemic strains. Scientists have been developing universal influenza vaccine strategies, including vaccines that target conserved areas of the influenza virus that remain relatively unchanged season-to-season. However, critical scientific questions remain unanswered and must be addressed to accelerate this research.

Meeting attendees noted the need for improved influenza surveillance (especially in certain regions and subpopulations), as well as a better characterization of how influenza viruses are transmitted. They also encouraged more research on immune responses to influenza vaccination and infection, including the impact of pre-existing immunity on responses to future vaccinations or influenza exposures. One way to address these questions, the report notes, would be to conduct long-term natural history studies that include people of various ages from different regions of the world. Such studies could also help define other factors that affect host immunity and delineate mediators of viral pathogenesis. Standardized human challenge models—studies in which healthy adult volunteers are purposely infected with influenza under careful medical supervision in an inpatient setting—could serve as another tool to help understand immunity to influenza and rapidly assess new vaccine candidates.

Meeting attendees discussed limitations in current influenza diagnostics, and the report calls for improved techniques to define and measure correlates of protection against influenza infection. They also debated the pros and cons of using various animal models to test vaccine candidates, study influenza transmission and better understand viral pathogenesis and the immune response to influenza. The report concludes by emphasizing the need for improved coordination among various scientific disciplines to prioritize and ultimately realize shared research goals.

Article

CI Paules et al. The Pathway to a Universal Influenza Vaccine. Immunity DOI: 10.1016/j.immuni.2017.09.007 (2017).

Who

NIAID Director Anthony S. Fauci, M.D., co-author of the report, is available for comment.

We would like to welcome Ellie to the lab. Stop by and say hello.

Americo has been selected to be this year’s recipient of the Outstanding Postdoctoral Mentor Award. This award was established in 2012 to recognize a School of Medicine and Dentistry postdoc for outstanding mentoring of undergraduate or graduate students and/or other postdocs.

Congratulations!

Dr. Minsoo Kim

Dean's Professorships were established in 1982 and are designated by the Dean to be assigned to individuals of outstanding research excellence. Dr. Kim is a Professor of Microbiology and Immunology in the Center for Vaccine Biology and Immunology, and of Pharmacology and Physiology, a position he has held since 2015. He has been a member of the SMD faculty since 2007.

Dr. Kim is an established scientist who has made notable contributions in the field of host immune response against virus infection and cancer. He is especially noted for his pioneering contributions to the development of the most advanced imaging techniques that enable real-time observations of dynamic immune responses. In addition to the real-time "detection" of host immune reaction, Dr. Kim also uses optical technology to actively "control" our immune response against cancer. Cancer immunotherapy is an exciting topic, as it involves stimulating a patient's own immune system to fight the malignancy. Although the concept has been around for 100 years, Dr. Kim is making it more relevant today by using a technology called "optogenetics" (optics + genetics) to try to improve the response rates for immunotherapy.

Join us at the Convocation on September 12th, 2017 (4pm in the Class of '62 Auditorium)

Taylor Moon received the 2017 Peer Mentoring Award from the Department of Microbiology and Immunology. This is an annual award chosen by students in the department in recognition of a student who is a positive role model for other students, advocates for students, encourages others’ intellectual growth, and offers professional guidance.

We congratulate Taylor for receiving this well-deserved honor.

Dr. Kihong Lim, Research Assistant Professor in Dr. Minsoo Kim’s Laboratory, has been chose by the American Lung Association as a recipient of the July 2017-June 2018 Biomedical Research Grant, for his project titled: “Innate Immune Responses in Influenza Virus-Infected Trachea.”

Kihong Lim has worked in Dr. Kim’s lab as a Staff Scientist since 2011, and was recently promoted to Research Assistant Professor. Kihong has had a huge impact in the Kim Lab, as he has been a key contributor to NIH-funded research programs. We are very excited to him establish his own research project and become independent in his future career.

Dr. Marta Lopez De Diego

Dr. Marta Lopez De Diego, Research Assistant Professor in the Topham Lab, receives University Research Award to further analyze NS1 protein variability in the current seasonal influenza A H1N1 and H3N2 viruses and characterize the effect of the identified mutations on evading host innate immune responses and in modulating viral pathogenesis The project is entitled “Role of NS1 mutations in interferon responses, inflammation and pathogenesis induced by seasonal human influenza A viruses,” and is a collaboration between Dr. Marta Lopez De Diego and Dr. Aitor Nogales Gonzalez in the at the University of Rochester.

The Elliott Lab received University Research Award to investigate the mechanisms and immunologic consequences of macrophage exhaustion resulting from immunotherapy-induced antibody-dependent cell phagocytosis. The project is entitled “Macrophage exhaustion as a novel mechanism of resistance to therapeutic mAbs,” and is a collaboration between the labs of Dr. Elliott and Dr. Clive S. Zent in the Wilmot Cancer Institute at the University of Rochester.

The science behind harnessing the immune system to fight cancer is complicated, but a University of Rochester Medical Center laboratory discovered a simple, practical way to use light and optics to steer killer immune cells toward tumors.

In a study published by the online journal Nature Communications, lead author Minsoo Kim, Ph.D., a UR professor of Microbiology and Immunology and a Wilmot Cancer Institute investigator, described his method as similar to "sending light on a spy mission to track down cancer cells."

Immunotherapy is different from radiation or chemotherapy. Instead of directly killing cancer cells, immunotherapy tells the immune system to act in certain ways by stimulating T cells to attack the disease. Several different types of immunotherapy exist or are in development, including pills called "checkpoint inhibitors" and CAR T-cell therapy that involves removing a patient's own immune cells and altering them genetically to seek and destroy cancer cells.

The problem, however, is that immunotherapy can cause the immune system to overreact or under-react, Kim said. In addition, cancer cells are evasive and can hide from killer T-cells. Aggressive tumors also suppress the immune system in the areas surrounding the malignancy (called the microenvironment), keeping T cells out.