Presentation Type
Oral Presentation
Category
STEM (science, technology, engineering, mathematics)
Abstract/Artist Statement
Crimean-Congo Hemorrhagic Fever Virus (CCHFV) is commonly transmitted by ticks and has a wide geographic distribution, being endemic throughout southern and eastern Europe, the Middle East, Asia, and Africa. Due to climate change, this range is even expanding northward. CCHFV causes a hemorrhagic disease characterized by initial non-specific illness (fever, muscle pains, nausea) followed by severe internal and external bleeding with a case fatality rate of 5-60%. As there is no licensed therapeutics or vaccines, there is great need for highly effective countermeasures. Recently, we have developed a self-replicating RNA-based vaccine which expresses two of the viral proteins: the CCHFV nucleoprotein (repNP) and glycoprotein precursor (repGPC) and is highly protective against a lethal viral challenge in mice.
We found that vaccination with this vaccine prevented disease and conferred 100% survival against a lethal CCHFV infection in mice. This vaccine significantly stimulated both antibody-producing B-cells and T-cells which kill infected cells. Our repNP vaccination primarily stimulated B-cells to produce anti-NP antibodies while repGPC primarily stimulated the T-cells. To confirm whether B-cells or T-cells are most responsible for protection, we vaccinated mice lacking B- or T-cells. While mice lacking T-cells survived, B-cell deficient mice only had ~40% survival indicating that the B-cells and antibodies are essential to confer protection. Currently, this vaccine is undergoing further preclinical testing in preparation for human clinical trials while ongoing studies are continuing to investigate how these antibodies protect against CCHFV so that we may improve additional and much needed CCHFV therapeutics.
This research was funded by the Intramural Research Program, NIAID, NIH.
Mentor Name
Heinrich Feldmann
Personal Statement
In 2017, the World Health Organization amended its list of high priority pathogens with pandemic potential to include Crimean-Congo Hemorrhagic Fever Virus (CCHFV). As we learned from the SARS-CoV-2 pandemic, it is important to prepare for potential outbreaks and lead research aimed at combatting these viruses before they spread across the globe. Currently, CCHFV is endemic across Europe, Asia, and Africa however, due to climate change, the viral tick vector is spreading ever northward, simultaneously increasing the number of those at risk and the need for effective vaccines and therapeutics. Recently, our lab developed a highly protective vaccine which is planned to enter human clinical trials and we are currently trying to optimize its protective efficacy as well as its manufacturability. Although the vaccine itself is a huge step towards pandemic preparedness, the work doesn’t stop there. This vaccine can also be used as a tool to uncover key aspects of CCHFV pathogenesis that inform development of further countermeasures. The vaccine protects primarily through antibodies aimed at the CCHFV nucleocapsid protein (NP), indicating that the NP may have an important role in causing disease. Therefore, we are using the vaccine to produce monoclonal antibodies against the NP in order to develop therapeutics. A vaccine is a great tool against viruses but therapeutics for those already infected or unable to get the vaccine are also needed. This work has been continuously inspiring as I realize the potential a vaccine has to protect the community in a variety of ways. The SARS-CoV-2 pandemic has no doubt increased the rates of vaccine hesitancy, to help ease these concerns I am excited to share my research with the community and explore not only how these vaccines protect but also how we can move forward in creating a safer and well-prepared society against future pandemics.
Leventhal oral presentation video
An RNA Vaccine Protects against Crimean-Congo Hemorrhagic Fever Virus Infection in Mice
UC 331
Crimean-Congo Hemorrhagic Fever Virus (CCHFV) is commonly transmitted by ticks and has a wide geographic distribution, being endemic throughout southern and eastern Europe, the Middle East, Asia, and Africa. Due to climate change, this range is even expanding northward. CCHFV causes a hemorrhagic disease characterized by initial non-specific illness (fever, muscle pains, nausea) followed by severe internal and external bleeding with a case fatality rate of 5-60%. As there is no licensed therapeutics or vaccines, there is great need for highly effective countermeasures. Recently, we have developed a self-replicating RNA-based vaccine which expresses two of the viral proteins: the CCHFV nucleoprotein (repNP) and glycoprotein precursor (repGPC) and is highly protective against a lethal viral challenge in mice.
We found that vaccination with this vaccine prevented disease and conferred 100% survival against a lethal CCHFV infection in mice. This vaccine significantly stimulated both antibody-producing B-cells and T-cells which kill infected cells. Our repNP vaccination primarily stimulated B-cells to produce anti-NP antibodies while repGPC primarily stimulated the T-cells. To confirm whether B-cells or T-cells are most responsible for protection, we vaccinated mice lacking B- or T-cells. While mice lacking T-cells survived, B-cell deficient mice only had ~40% survival indicating that the B-cells and antibodies are essential to confer protection. Currently, this vaccine is undergoing further preclinical testing in preparation for human clinical trials while ongoing studies are continuing to investigate how these antibodies protect against CCHFV so that we may improve additional and much needed CCHFV therapeutics.
This research was funded by the Intramural Research Program, NIAID, NIH.