“Winning a SPARK Award would mean a lot to me because it would mean people understand and care about my research on infectious diseases. It would also give me the experience and confidence to apply for an independent young investigator grant which is key for my future career.”
What if we could halt the spread of dengue, the most prevalent mosquito-borne virus, through improved vaccine development?
FUNDED: JANUARY 2021
FUNDED BY: The generosity of Barbara Donnell, Bill Passey & Maria Silva, and various 2020 SPARK Donors.
What was the goal of your SPARK project?
Dengue virus affects 3.6 billion people worldwide, and the severe form of dengue has been known to kill thousands of children annually for decades. We aimed to identify how prior exposure to another flavivirus, called Japanese encephalitis virus (JEV), modulates disease severity in
patients with acute dengue infection.
My SPARK project began as a first step to determine whether pre-existing immunity to JEV can modulate dengue infection and disease severity, and thus understand the influence of pre-exposure to closely related viruses on subsequent infection. We planned to collect suspected dengue cases in partnering hospitals in Nepal and perform laboratory experiments to confirm dengue infection.
The long-term goal of this research is to guide vaccine design by exploring the host immune response of individuals with prior immunity to a closely related virus and define which components of the immune response induced protection or pathogenesis.
Did you face any challenges?
Although we anticipated that the pandemic would delay patient enrollment or reduce the numbers of samples for the study, we did not expect that the second wave of COVID-19 in Nepal during 2021 would prevent the enrollment of dengue patients. All of our partnering hospitals were designated as COVID-19 centers, in addition lockdowns and illness among the staff added to the challenge of enrolling suspected dengue patients. However, I was able to pivot and use samples collected in 2017. These samples had some limitations but I was ultimately able to move forward with my project.
SPARK project results:
Although, we were not able to conclude on the association between pre-existing immunity to JEV and dengue disease severity due to the small sample size, we were able to (1) detect and classify dengue infection in 2017 in Nepal, (2) determine and confirm the presence of prior-exposure to JEV in patients experiencing dengue infection, (3) establish and strengthen the collaboration between LJI and Nepal to successfully continue our research work (in terms of legal documents and experiments), (4) substantially advance our understanding of cross-reactive immunity, (5) generate meaningful preliminary data for grants, including NIH opportunities, (6) prepare the team in Nepal for the future dengue sample collection in 2022 (predicted outbreak year based on dengue cycle in Nepal). Nepal represents a unique model system to address many critical questions related to immunology controlling or exacerbating dengue virus, flaviviruses, and emerging infectious diseases.
What’s next for this project?
My experience with the SPARK program allowed me to realize how ambitious the project I proposed was and the different steps (paperwork and technical adjustments) needed to start working on a pathogen such as JEV. The SPARK award set up a critical framework for this new type of research at LJI. The results generated during this project are important and will be used as preliminary data to apply for NIH grants and write a manuscript.
What’s next for Annie?
I would like to continue studying infectious diseases, with a focus on emerging and neglected viruses. My expertise right now is on flaviviruses and coronaviruses, but I do not intend to restrict my research interests to only these virus families in the future. I am open to opportunities, but ultimately I would like to establish my own lab that focuses on host immune responses to viral infection.