By studying the novel coronavirus from many angles and disciplines, UW–Madison is at the forefront of fighting COVID-19. School of Veterinary Medicine researchers are leading several of these studies, helping to address major challenges of the disease and advance vaccine, treatment, and containment strategies.
The work highlights the school’s long history of international leadership in infectious disease research and the field of veterinary medicine’s critical contributions to tackling urgent health challenges, be they human or animal.
“COVID-19 has obviously had a devastating effect on the health and welfare of people around the world. Our faculty are engaged in fundamental and applied research to better understand this virus and speed development of an effective vaccine — the two essential requirements to more effectively manage, and eventually emerge from, the current pandemic,” says Dale Bjorling, the school’s associate dean for research and graduate training.
An international collaboration of virologists at the School of Veterinary Medicine and the vaccine companies FluGen and Bharat Biotech has begun the development and testing of a unique vaccine against COVID-19 called CoroFlu.
CoroFlu will build on the backbone of FluGen’s flu vaccine candidate known as M2SR, based on an invention by SVM virologists and FluGen co-founders Yoshihiro Kawaoka and Gabriele Neumann. Kawaoka’s lab will insert gene sequences from SARS-CoV-2, the novel coronavirus that causes the disease COVID-19, into M2SR so that the new vaccine will also induce immunity against the coronavirus.
Following refinement of the CoroFlu vaccine concept and testing in laboratory animal models at UW–Madison, Bharat Biotech in India will then begin production scale-up for safety and efficacy testing in humans. CoroFlu could be in human clinical trials by September.
“To confront a global challenge, this is collaborative discovery at its best,” says Erik Iverson, CEO of the Wisconsin Alumni Research Foundation (M2SR includes technology exclusively licensed through the organization).
Adel Talaat, a professor of pathobiological sciences in the School of Veterinary Medicine, and his lab are also working on a potential vaccine against COVID-19, based on technology previously developed to combat another kind of coronavirus that causes disease in poultry. That vaccine, a benefit to agriculture, is currently in the process of being licensed. Talaat is an expert on nanotechnology-based vaccines for human and animal diseases.
Cats and COVID-19
Professor Yoshihiro Kawaoka led a study published in May in the New England Journal of Medicine reporting that in the laboratory, cats can readily become infected with SARS-CoV-2, the virus that causes COVID-19, and may be able to pass the virus to other cats. Importantly, none of the SARS-CoV-2-infected cats showed symptoms of illness.
Their findings suggest cats may be capable of becoming infected with the virus when exposed to people or other cats positive for SARS-CoV-2. It follows a study published in Science that also showed cats (and ferrets) could become infected with and potentially transmit the virus. The virus is known to be transmitted in humans through contact with respiratory droplets and saliva.
“If [people] are quarantined in their house and are worried about passing COVID-19 to children and spouses, they should also worry about giving it to their animals,” says Peter Halfmann, a research professor who helped lead the study.
Sandra Newbury, director of the UW–Madison Shelter Medicine Program, based in the School of Veterinary Medicine, is leading a research study in several states in the U.S. to test animal shelter cats that might have previously been exposed to human COVID-19 cases.
Newbury has worked with the CDC and the American Veterinary Medical Association to develop recommendations for shelters housing potentially exposed pets, which they may do while owners are hospitalized or otherwise unable to provide care because of their illness.
“Animal welfare organizations are working very hard in this crisis to main-tain the human-animal bond and keep pets with their people,” says Newbury.
For cats the risk of natural infection from exposure to SARS-CoV-2 seems to be quite low, Newbury says. Of the 22 animals the program has tested, none have had positive polymerase chain reaction tests for the virus.
Protective Immunity and Potential Treatments
In June, Kawaoka and Clinical Assistant Professor Samantha Loeber also published research in the Proceedings of the National Academy of Sciences showing that in Syrian hamsters, prior infection with the SARS-CoV-2 virus provides protection against reinfection, and treatment with convalescent serum limits virus replication in their lungs. The study demonstrates that hamsters share important features of human COVID-19 disease, and are a useful model for researchers trying to understand SARS-CoV-2 and in evaluating vaccines, treatments, and drugs against the disease it causes.
To determine whether hamsters developed antibodies against SARS-CoV-2 that protected them from reinfection, the researchers administered another round of the virus to a number of previously infected animals about three weeks following initial infection and were unable to detect virus in their respiratory tracts.
“The animals all possessed antibodies and did not get sick again, which suggests they developed protective immunity,” says Halfmann. “But we still can’t say how long this protection lasts.”
In early April, researchers across the U.S., including at the UW School of Medicine and Public Health and UW Health, initiated a clinical trial to examine whether the antibody-bearing component of blood — the plasma or sera — from recovered COVID-19 patients could be given to sick patients to assist in their recovery. While convalescent plasma has been used in other disease outbreaks, it remains poorly understood as a treatment.
So, Kawaoka’s team extracted convalescent sera from previously sick hamsters and pooled it together. They infected new hamsters with SARS-CoV-2 and then gave them this antibody-laden sera either one day or two days following infection. Hamsters that received treatment within a day of infection had much lower amounts of infectious virus in their nasal passages and lungs than those given a mock treatment. Those that received sera
on day two showed a less appreciable benefit, though they still had lower levels of virus compared to control animals.
Finally, the research team also obtained the first images of the internal features of the SARS-CoV-2 virus that aid its ability to replicate, or make copies of itself, in host cells. This, Kawaoka says, warrants further study.
Genetic Surveillance of Coronavirus Spread
American society may have closed down during the pandemic, but for Thomas Friedrich, the key to beating COVID-19 lies in being open — not open for business but open for discovery.
“We want to find ways that scientists across institutions and the world can collaborate to find the best vaccine, the best treatments, the best approaches,” Friedrich says.
A virologist in the School of Veterinary Medicine, Friedrich is part of a collection of researchers — 142 of them at more than 30 institutions — calling themselves the CoVen. They’re putting their skills together to study coronavirus and sharing all they find, freely, among the entire group. “It’s all of us in humanity against the virus, so we need to pool our resources,” he says.
Friedrich and his team are tracking genetic changes in the novel coronavirus that occur as it spreads from person to person. These changes are like signatures that allow scientists to follow how the coronavirus spreads through the world. They can help determine whether an outbreak is due to community spread or an introduction of coronavirus into a community due to travel.
Comparing samples of the virus from people in Wisconsin to a global database, Friedrich and his colleagues see suggestions that the outbreak in the Milwaukee area differs in some ways from the outbreak in and around Madison. From preliminary data in April, it appeared that most infections in Dane County were introduced from Europe, probably from returning travelers, whereas a large proportion of Milwaukee County cases are more closely related to viruses from Asia.
The distinct genetic signatures in viruses from the Madison and Milwaukee areas “suggests to us that there’s been some success in the travel restrictions” and social distancing guidelines, said Friedrich, because it means the viruses his team have characterized were not being passed from person-to-person between the two regions.
View online: In April, Friedrich spoke about his research in a UW Now Livestream.
Kelly April Tyrrell, Eric Hamilton, Meghan Lepisto and the Wisconsin Alumni Association contributed to this story.
*Note: The photos of researchers on these pages were taken in March before public health protocols encouraged or mandated face coverings to reduce the risk of COVID-19 transmission. Currently, all UW–Madison employees are required to wear a face mask while in campus buildings. This is in addition to other mandatory health protocols.