As the world continues to fight the COVID-19 pandemic, research teams worldwide are working towards making a successful vaccination for the disease. At the University, teams have left behind ongoing research efforts in order to bring their attention to the novel coronavirus instead. William Petri, professor of medicine and infectious disease expert, is leading a team that has moved from 25 years of amoebic dysentery vaccine research to vaccine trials in COVID-infected mice.
Peter Kasson, associate professor of molecular physiology and biomedical engineering, is using knowledge from years of influenza and Zika virus research to evaluate how the virus infects cells and how coronavirus antibodies work.
According to Kasson, there are four types of treatment for COVID-19 — vaccines, antiviral drugs, immunotherapies and other drugs that make the body less susceptible to infection. In his current research, Kasson is focusing on how antibodies work to protect against coronavirus.
“Vaccines train your body to make antibodies and immune cells to fight the virus. Antiviral drugs try to stop key proteins in the virus from functioning,” Kasson said.
Additionally, Kasson explained that immunotherapies can consist of virus antibodies that are administered through veins, as well as other drugs which change the body’s immune response. In terms of making the body less susceptible to infection, other drugs can decrease the body's production of proteins that the virus infects.
Petri, alongside a group of 20 scientists, is spearheading the first in the list of treatments — a vaccine. The team is using knowledge from amoebic dysentery research, which has been supported by the Biomedical Advanced Research and Development Authority, in hopes that this research could quickly transition to a much needed vaccine in the coming months, such as one for the coronavirus.
“We were the group that identified … what is called immune correlates of protection,” Petri said. “So there is an antibody response against the surface protein of the [amoeba dysentary] parasite that is associated with being immune to reinfection.”
Through collaboration with the Infectious Disease Research Institute in Seattle, Petri and his team have identified robust antibody responses for the amoebic dysentery parasite in mucosal sites, which are also places where COVID-19 is known to replicate.
After successfully growing SARS-coronavirus-2 in their lab, the team is using the exact same approach for the amoebic dysentery vaccine, though they have swapped the amoebic protein for the coronavirus protein. The group of scientists is currently vaccinating mice and will be able to assess the neutralizing antibody response by the end of this month.
There is only one source in the world for the specific transgenic mice used during this testing, Petri explained. The mice overexpress the human H2 enzyme, which is the receptor for coronavirus, making them especially susceptible to COVID-19.
“U.Va. will probably be one of the very first places in the world to have an established mouse model for COVID-19,” Petri said. “You want to do it first in an animal model to understand how to optimize its effectiveness, and so that development of the mouse model will be enormous.”
Kasson — who specializes in looking at how viruses bind to receptors in the body — is helping measure the neutralizing antibody.
“We will design a mucosally-targeted vaccine candidate to protect against SARS-CoV-2 and future related viruses,” Kasson said in an email to The Cavalier Daily. “By doing so, we hope to contribute to preventing not only COVID-19 disease in vaccinated individuals, but also help interrupt transmission to others.”
According to Kasson, this work involves several pieces. One, which Petri’s group is doing, is designing a vaccine platform to elicit mucosal immunity and actually performing the vaccination studies. Another is evaluating how the antibodies work, which Kasson is working on. And the two groups are collaborating on designing virus antigens to obtain the best immunity.
Petri is currently writing grants to the National Institutes of Health to increase their funding in order to continue the animal model trials. Using this research, the best treatments to produce the best immune response in COVID-positive patients can be determined. This testing looks at the different ways the vaccine can be administered, the best vaccine dosage and the interval at which the vaccine should be repeatedly given.
In addition to creating the mouse model, Petri and his team are collecting plasma from COVID-19 patients at the University Hospital at the time of diagnosis in order to predict the more severe coronavirus cases, allowing doctors to treat patients appropriately.
Jeffrey Sturek, medical professor of pulmonary and critical care, helped coordinate this COVID-19 biorepository.
Prior to the pandemic, Sturek had been working on lung injury and fibrosis and immunology of those in both mice and humans and had already been collecting patient samples under different research projects to study chronically ill patients.
“[With the biorepository], we can sort of understand the biology of the disease process and look at things like biomarkers for severity of illness or understanding the immune response to the infection so that we can design better diagnosis and treatment,” Sturek said.
Sturek is also a co-principal investigator in a local clinical trial called the convalescent immune plasma treatment trial. The treatment takes plasma from a patient previously infected with COVID-19 who has created antibodies to fight off the virus. 28 days after the illness, that plasma is tested to ensure there are antibodies against COVID-19 present, at which point the plasma is administered to currently infected patients in an attempt to mitigate the severity of disease.
Despite the extensive progress that has been made, Petri does not expect the University to be one of the first institutions to produce a vaccine. Intead, he suspects that the pharmaceutical companies of Johnson & Johnson or Pfizer, or Oxford University will have a vaccine on the market first.
“Our approach is unique in our ability to make antibodies in mucosal sites,” Petri said. “There will be a role for our vaccine, maybe it will offer some advantages over the very first vaccines that come to market.”
No matter the timelines or outcomes of COVID-19 research, Sturek says that the important thing to take home is that this is not going to be the last pandemic. Though he hopes that the coronavirus is a unique experience, Sturek believes that what is being learned and researched now will apply to other pandemics in the future. This knowledge will not only allow the globe to be better prepared epidemiologically, but also when it comes to dealing with specific treatments for severely ill patients.
“I think that's part of the ongoing research,” Sturek said. “Not just dealing with this one, but
what comes down the pipeline next.”
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