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.

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.