Enlisting Help to Combat Powassan Virus
The COVID-19 pandemic has drawn attention to other emerging viruses with the potential to cause outbreaks in humans. “One of the most important is the critical need for a ‘prototype pathogen approach,’ in which a representative virus is studied to prepare for future outbreaks of any member in the same family,” said Dr. Kartik Chandran, professor of microbiology & immunology.
This premise is the inspiration for Kartik’s collaboration with the United States Military Academy West Point (“West Point”) to study Powassan virus (POWV), a flavivirus in the same family as the Dengue and Zika viruses. “Addressing POWV could pave the way for developing other flavivirus treatments,” he noted.
An Opportunity to Expand Knowledge
POWV is a tick-borne virus found primarily in North America. While infection with POWV is generally uncommon, severe cases can lead to brain infection and death. There is currently no effective treatment available. “POWV is not often diagnosed,” noted Dr. Emily Miller, assistant professor of medicine and of microbiology & immunology and an M.D./Ph.D. alumna in Einstein’s class of 2014, who is leading the study. “And it likely is often confused with the more prominently known Lyme disease, which is why there is a need to learn more.”
West Point has a special interest in effective POWV screening: during the summer, many of their training exercises take place in woods where there is a large deer tick population. “This means West Point cadets are at high risk for tick bites but at lower risk for severe POWV infection, since they are young and healthy,” said Emily. “Therefore, there may be a significant amount of undetected POWV infection going unrecognized.”
She explained, “Identifying antibodies against POWV could be immensely helpful toward developing an effective therapeutic.”
An antibody is a protein that binds specifically to a particular target – in this case, a part of the virus. The goals of the Einstein-West Point collaboration are twofold: to determine the prevalence of POWV and to identify an antibody that can be developed into a treatment.
In March, six cadets from West Point visited the labs of Dr. Chandran and a close collaborator of his, Dr. Jonathan Lai, Dan Danciger Professor of Biochemistry. Two of these cadets – Zoey DiPasqua and Justin Jones – then returned for three weeks in July to learn how to perform an ELISA (enzyme-linked immunosorbent assay), a method for detecting specific proteins in a sample.
Using blood drawn previously from cadets as part of their matriculation, Zoey and Justin optimized the ELISA protocol under Emily’s guidance to test for evidence of prior POWV infection or exposure. The cadets also received hands-on mentoring from two Einstein students– fifth-year Ph.D. student Georgia Fallon (Lai lab) and fifth-year MSTP student Alexandra Tse (Chandran Lab).
“At West Point, we taught the cadets the ELISA protocol and basic experimental design, then at Einstein we helped them practice,” noted Georgia.
She also described the advantages of the collaboration for her own graduate training. “Getting to mentor young scientists who are so motivated has invigorated my excitement about my own project.”
Armed with this training, Zoey and Justin will lead a prospective study back at West Point. “The plan is to take blood samples from cadets at the beginning and end of their first year and determine if anyone had contracted POWV in that time. This will offer information about the regional prevalence of POWV,” said Zoey.
Military Precision
The cadets worked quickly, and, in just three weeks, they identified two seropositive patient samples from banked West Point samples—which showed detectable levels of circulating antibodies against the virus—and determined the best serum dilution for an accurate test for POWV.
“West Pointers are used to making commitments, so we were ready to jump in when we got here. All this work puts us leagues ahead of where we were before we arrived,” said Justin.
“Justin and Zoey were a quick study, and it was really great to work with them,” said Alex.
Both cadets are life science majors hoping to become army physician-scientists, so they were eager to kickstart a program addressing a potential public health concern that could affect West Point cadets.
“This level of immersion was exactly what we were going for,” Justin said, “and it really gets your brain going about how to use what we learned to eventually tackle other flaviviruses as well.”
Zoey agreed, noting “Future cadets can keep moving this work forward even after we graduate.”
Cadets who test positive for POWV antibodies will have their blood drawn again so that POWV-binding antibodies can be isolated from their immune cells, which can then possibly be developed into a treatment.
Getting Out in Front of a Problem
While POWV may not be a widespread health concern currently, there are significant advantages to addressing the virus early.
“POWV is probably more common than we realize because we don’t test for it enough, and, with climate change leading to warmer winters, tick-borne illnesses are on the rise,” noted Emily.
Kartik, who also holds the Gertrude and David Feinson Chair in Medicine and is a Harold and Muriel Block Faculty Scholar in Virology, offered an even broader benefit to conducting POWV research, noting, “Odds are, we won’t be able to predict all future viral outbreaks. We got spectacularly lucky that coronaviruses similar to COVID-19 were already being studied, but it doesn’t have to be like that. If we’re smart, we can be prepared even for the unknown unknowns.”
Jon added, “We’re talking about pandemic prevention now. We have to evolve our thinking from what’s killing us today to what could kill us in twenty years.”
Posted on: Wednesday, November 29, 2023