Ebola vaccine inches toward human clinical trials

A whole-virus vaccine to confront Ebola, the rare but often fatal hemorrhagic disease that periodically erupts in sub-Saharan Africa, may soon be one step closer to the clinic.

Yoshihiro Kawaoka

With the help of experts at Waisman Biomanufacturing, within the University of Wisconsin-Madison’s Waisman Center, UW-Madison School of Veterinary Medicine Professor Yoshihiro Kawaoka will lead a $3 million effort to produce as many as 1,000 doses of an experimental vaccine that has already been proven to work safely in monkeys.

“The goal is to produce a safe and effective vaccine against Ebola virus for people,” says Kawaoka, a world expert on Ebola and influenza. The vaccine is planned for use in a phase 1 clinical trial in Japan and is the only whole-virus Ebola vaccine candidate under development.

It will be produced at Waisman Biomanufacturing, a specialized facility whose mission is to help translate scientific discovery into early-stage clinical trials. The staff of the facility provides expert help with manufacturing processes, quality control and overall product development in addition to regulatory support.

Ebola virus swarms the surface of a host cell in this electron micrograph. Like most viruses, Ebola requires the help of a host cell to survive and replicate. Photo by Takeshi Noda, University of Tokyo.

“Waisman Biomanufacturing produces many different types of biopharmaceutical products, keeping our range of expertise broad in order to serve any University of Wisconsin investigator who has a biological that they wish to bring into the clinic,” says Carl Ross, the facility’s managing director. “We have made many prophylactic and therapeutic vaccines for use in human clinical trials.”

The technology behind the new Ebola vaccine was devised nearly a decade ago by Peter Halfmann, a research scientist in Kawaoka’s lab who is also an expert on the Ebola virus. It is known as “Delta VP30,” and is a form of Ebola virus that is noninfectious and safe to work with under routine laboratory conditions such as those at Waisman Biomanufacturing. The virus is missing a critical gene – one of only eight genes that make up the virus genome – that makes a protein the virus needs to reproduce in host cells.

Vaccines work by exposing the immune system to viruses or parts of viruses. The Delta VP30-based vaccine may offer better protection against Ebola virus than others in the pipeline, Kawaoka says, because it is a whole-virus vaccine. Other Ebola vaccine candidates use vector viruses to ferry a single Ebola protein, a surface antigen, to prime the immune system.

“Here, we have a whole-virus vaccine that presents all the viral proteins to the immune system, which may result in increased and broadened immune responses compared to vaccines that present only a single viral antigen to the immune system,” Kawaoka explains.

The need for an Ebola vaccine is acute. Periodic outbreaks of the disease in sub-Saharan Africa, including an epidemic between 2013 and 2016, caused major loss of life and serious economic disruption in the three countries where it occurred: Sierra Leone, Guinea and Liberia.

The new vaccine project will be the subject of an informational meeting to be held Feb. 27 at 4:30 p.m. at the Friends of the Waisman Center Auditorium on the first floor of the West Annex. The Waisman Center is located at 1500 Highland Ave. Free parking is available after 4:30 p.m. in Lot 82, behind the Waisman Center and accessible from Highland Avenue.

By Terry Devitt, University Communications/ February 21, 2018

This story was first published at news.wisc.edu.

Saving our planet to save ourselves

Howard Frumkin looks at challenges and opportunities in planetary health

What do you believe in? Leaving a livable world for our children and grandchildren? Not wasting what we’ve been given? Responsibility?

Likely, you believe in all three. For Howard Frumkin, professor and former dean of the University of Washington School of Public Health and former director of the National Center for Environmental Health at the Centers for Disease Control and Prevention, finding those shared beliefs is critical to moving beyond ideological divides to ensure planetary health for humans as well as the world we live in.

Frumkin will discuss “Planetary Health: Protecting Our World to Protect Ourselves,” at 5:30 p.m., Thursday, February 15, in the Great Hall at Memorial Union. A panel of University of Wisconsin-Madison science and humanities scholars—Lyric Bartholomay from Veterinary Medicine, Maureen Durkin from Population Health Sciences, Rick Keller from the International Division, Gregg Mitman from Medical History and the Nelson Institute, Jonathan Patz from the Global Health Institute (GHI) and Monica White from Environmental Sociology and the Nelson Institute—will respond to his remarks.

The free program will be followed by a paid reception. All are welcome. Registration is requested. The evening is hosted by the UW-Madison Global Health Institute and co-sponsored by the International Division, Office of Sustainability and Nelson Institute for Environmental Studies.

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GHI Associate Director for Research Tony Goldberg’s TEDxUWMadison: Discovering Pathogens and the Pathways by Which They Emerge

In this talk, Goldberg talks about pathogens and the role they have in human evolution.

Goldberg is Professor of Epidemiology at the University of Wisconsin Madison School of Veterinary Medicine, John D. MacArthur Research Chair at UW-Madison, and Associate Director for Research at the UW-Madison Global Health Institute. He received his B.A. from Amherst College (1990, Biology and English), his Ph.D. from Harvard University (1996, Biological Anthropology), and his Doctor of Veterinary Medicine and MS in Epidemiology from University of Illinois at Urbana-Champaign (2000).

Goldberg studies the ecology, epidemiology and evolution of infectious disease. His research combines field and laboratory studies to understand how disease-causing agents are transmitted among hosts, across complex landscapes, and over time. He combines these techniques with methods from the social sciences to understand the root drivers of disease emergence in real world settings. Goldberg strives to discover generalized mechanisms of pathogen transmission, emergence, and evolution. His overarching goal is to improve the health and wellbeing of animals and people while helping to conserve the rapidly changing ecosystems we share. This talk was given at a TEDx event using the TED conference format but independently organized by a local community

In the heart of devastating outbreak, research team unlocks secrets of Ebola

a vial is labeled and prepared to hold blood from an Ebola patient in Sierra Leone. Researchers from the UW-Madison, the University of Tokyo and the University of Sierra Leone will compare blood from those who died of the virus to those who survived and those who never got sick to try and develop treatment. (Photo courtesy of Kawaoka Lab.)

This story appeared first at news.wisc.edu.

In a comprehensive and complex molecular study of blood samples from Ebola patients in Sierra Leone, published today (Nov. 16, 2017) in Cell Host & Microbe, a scientific team led by the University of Wisconsin–Madison has identified signatures of Ebola virus disease that may aid in future treatment efforts.

Conducting a sweeping analysis of everything from enzymes to lipids to immune-system-associated molecules, the team — which includes researchers from Pacific Northwest National Laboratory (PNNL), Icahn School of Medicine at Mount Sinai, the University of Tokyo and the University of Sierra Leone — found 11 biomarkers that distinguish fatal infections from nonfatal ones and two that, when screened for early symptom onset, accurately predict which patients are likely to die.

With these results, says senior author Yoshihiro Kawaoka, a virology professor at the UW–Madison School of Veterinary Medicine, clinicians can prioritize the scarce treatment resources available and provide care to the sickest patients. Kawaoka is also a member of the GHI Advisory Committee and received a 2017 GHI Seed Grant to catalog viruses circulating among West Africans with an eye to improving diagnoses, identifying new viruses and, potentially, preventing the next epidemic.

Studying Ebola in animal models is difficult; in humans, next to impossible. Yet, in Sierra Leone in 2014, a natural and devastating experiment played out. In September of that year, an Ebola outbreak like no other was beginning to surge in the West African nation. By December, as many as 400 Ebola cases would be reported there each week.

That fall, Kawaoka sought access to patient samples. He has spent a career trying to understand infectious diseases like Ebola — how do they make people sick, how do bodies respond to infection, how can public health officials stay at least a step ahead?

“Here, there is a major outbreak of Ebola. It is very rare for us to encounter that situation,” says Kawaoka, who is also a professor of virology at the University of Tokyo.

Yet blood samples were proving difficult to obtain and people continued to die.

Then, just weeks before Christmas, Kawaoka learned about a colleague in his very own department at UW–Madison, a research fellow from Sierra Leone named Alhaji N’jai, who was producing radio stories for people back home to help them protect themselves from Ebola. The pair forged a fortuitous partnership.

“He knows many people high up in the Sierra Leone government,” says Kawaoka. “He is very smart and very good at explaining things in lay terms.”

By Christmas, Kawaoka, N’jai and Peter Halfmann, a senior member of Kawaoka’s team, were in Sierra Leone.

“On the first trip, Alhaji took me to Parliament and we talked to a special advisor to the president, then the vice chancellor of the University of Sierra Leone,” says Kawaoka. “We got the support of the university, which helped us identify military hospitals and provided space. We went to the Ministry of Health and Sanitation and the chief medical officer and we explained what we hoped to do.”

Yoshihiro Kawaoka, professor of pathobiological sciences at the UW-Madison School of Veterinary Medicine, meets with Ekundayo Thompson, vice chancellor of the University of Sierra Leone, while in the African nation to establish a partnership to study and fight Ebola while improving the research capacity and infrastructure of the University of Sierra Leone. (Photo courtesy of the Kawaoka Lab.)

By February of 2015, Kawaoka and other select senior researchers on his team, including Amie Eisfeld, set up a lab in a military hospital responding to the outbreak in the capital city of Freetown (the researchers never entered patient wards). With the approval of patients and the government of Sierra Leone, health workers collected blood samples from patients after they were diagnosed with Ebola and at multiple points thereafter.

They obtained 29 blood samples from 11 patients who ultimately survived and nine blood samples from nine patients who died from the virus. The samples were transported to the lab where Kawaoka’s experienced and expertly trained team inactivated the virus according to approved protocols. Blood samples were subsequently shipped to UW–Madison and partner institutions for analysis.

For comparison, the research team also obtained blood samples from 10 healthy volunteers with no exposure to Ebola virus.

SIDEBAR: Video reaches ‘Spiderman’ audience with Ebola messaging

“Our team studied thousands of molecular clues in each of these samples, sifting through extensive data on the activity of genes, proteins and other molecules to identify those of most interest,” says Katrina Waters, a biologist at PNNL and a corresponding author of the study. “This may be the most thorough analysis yet of blood samples of patients infected with the Ebola virus.”

The team found that survivors had higher levels of some immune-related molecules, and lower levels of others compared to those who died. Plasma cytokines, which are involved in immunity and stress response, were higher in the blood of people who perished. Fatal cases had unique metabolic responses compared to survivors, higher levels of virus, changes to plasma lipids involved in processes like blood coagulation, and more pronounced activation of some types of immune cells.

UW-Madison’s Yoshihiro Kawaoka, Peter Halfmann and Alhaji Njai stand outside of a military hospital with Foday Sahr, a Sierra Leone military official and chair of microbiology at the University of Sierra Leone. Ebola patients are treated at many of the country’s military hospitals like the Joint Medical Unit.
(Photo courtesy of the Kawaoka Lab.)

Pancreatic enzymes also leaked into the blood of patients who died, suggesting that damage from these enzymes contributes to the tissue damage characteristic of fatal Ebola virus disease.

And, critically, the study showed that levels of two biomarkers, known as L-threonine (an amino acid) and vitamin D binding protein, may accurately predict which patients live and which die. Both were present at lower levels at the time of admission in the patients who ultimately perished.

“We want to understand why those two compounds are discriminating factors,” says Kawaoka. “We might be able to develop drugs.”

When Ebola virus leads to death, experts believe it is because of overwhelming viral replication. Symptoms of infection include severe hemorrhaging, vomiting and diarrhea, fever and more.

Kawaoka and his collaborators hope to better understand why there are differences in how patients’ bodies respond to infection, and why some people die while others live. The current study is part of a larger, multicenter effort funded by the National Institutes of Health.

“This may be the most thorough analysis yet of blood samples of patients infected with the Ebola virus.”

Katrina Waters

“The whole purpose is to study the responses of human and animal bodies to infection from influenza, Ebola, SARS and MERS, and to understand how they occur,” Kawaoka explains. “Among the various pathways, is there anything in common?”

In the current Ebola study, the team found that many of the molecular signals present in the blood of sick, infected patients overlap with sepsis, a condition in which the body — in response to infection by bacteria or other pathogens — mounts a damaging inflammatory reaction.

And the results contribute a wealth of information for other scientists aimed at studying Ebola, the study authors say.

Kawaoka says he is grateful to UW–Madison, University Health Services and Public Health Madison and Dane County for assistance, particularly with respect to his research team’s travel between Madison and Sierra Leone. Each provided protocols, monitoring, approval and other needed support during the course of the study.

“I hope another outbreak like this never occurs,” says Kawaoka. “But hopefully this rare opportunity to study Ebola virus in humans leads to fewer lives lost in the future.”

By Kelly April Tyrell, UW communications/ November 16, 2017



2018 Global Health Symposium

The Global Health Institute at the University of Wisconsin-Madison is pleased to welcome Professor Susan Paskewitz as the keynote speaker for the 14th annual Global Health Symposium: Advancing Health in Uncertain Times. The symposium begins at 4:30 p.m., Tuesday, April 10, 2018.

Paskewitz is professor and chair of the Department of Entomology in the College of Agricultural and Life Sciences. She also is co-director of the Upper Midwestern Center of Excellence for Vector-Borne Disease funded by the Centers for Disease Control and Prevention and a member of the GHI Advisory Committee. Her research focuses on medically important arthropods, including ticks and mosquitoes, and the human pathogens they transmit. She also teaches classes in global health and medical entomology.

The annual symposium provides a forum for the UW-Madison global health community to showcase recent work and connect with each other. The evening includes oral and poster presentations and a closing panel on a global health hot topic.

Watch this page for more details and registration information.

Call for abstracts

Deadline extended to: February 19, 2018

The call is open to members and partners of the UW-Madison community who are addressing global health and disease. From basic research to education to applied projects in the field, the symposium hopes to showcase the full spectrum of UW-Madison global health activity. We encourage and welcome presentations from all disciplines—from arts, agriculture, and business, to education, engineering, and humanities, to all of the health sciences and more. 

Following the keynote address, selected oral presenters will deliver their work in 15-minute (including time for questions), concurrent sessions. Posters will be available for viewing all evening, and a poster session follows the presentations. Hors d’oeuvres will be served during the networking reception that closes the evening.

Abstract Submission Form


Apply now for 2018 global health grants

The University of Wisconsin-Madison Global Health Institute (GHI) is pleased to announce the application period is open for its 2018 grants and awards. This competitive grant program is designed to support global health efforts of faculty, staff and graduate students across campus, fostering the Wisconsin Idea locally and globally.

This year, the Institute will offer a new grant, the Henry Anderson III Graduate Student Award in Environmental, Occupational and Public Health, in addition to Graduate Student Research Awards, Visiting Scholar Awards and Faculty and Staff Travel Awards. There will be no Seed Grant awards in 2018.

An expert on environmental and occupational disease, public health, epidemiology, disease and exposure surveillance, Henry Anderson III, M.D., is an adjunct professor in the Department of Population Health and former chief medical officer for the Wisconsin Division of Public Health. With the graduate student award, he hopes to support students pursuing research in the area of environment, occupation and global health.

The deadline for GHI grant applications is 11:59 p.m. January 29, 2018.

  • Henry Anderson III Graduate Student Award in Environmental, Occupational and Public Health supports graduate students interested in pursuing research in those topic areas. Application information is available here.
  • Graduate Student Research Awards supports doctoral students pursuing work in any relevant discipline whose graduate work will enhance global health activities on the UW-Madison campus and beyond. Grants of up to $5,000 each will be awarded. Application information is available here.
  • Visiting Scholar Awards brings visitors to UW-Madison who substantially enhance global health activities on campus in collaboration with a sponsoring UW-Madison faculty member or faculty team. Grants of up to $8,000 each will be awarded. Application information is available here.
  • Faculty and Staff Travel Awards are available for UW-Madison faculty and staff who are GHI affiliates. They can be used for international travel related to educational and research activities. Grants of up to $2,500 each will be awarded. Application information is available here.

To learn more about previous grant recipients, visit the global health research pages. For more information about the grants and grant process, contact the Global Health Institute, 265-9299.

By Ann Grauvogl/ November 9, 2017