“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.”
How does prior exposure to closely-related viruses contribute to protection or disease during subsequent infection with a related virus?
FUNDED: JANUARY 2021
FUNDED BY: the generosity of Barbara Donnell, Bill Passey & Maria Silva, and 2020 Various Donors
Dengue virus is the cause of the most prevalent mosquito-borne viral diseases in humans, impacting 3.6 billion people worldwide and the most severe form of dengue has been killing thousands of children annually for decades. Vaccination saves millions of lives every year and is one of the most effective approaches for eradicating/containing diseases. However, Dengvaxia, the only dengue vaccine that has been approved for human use, has multiple major problems. It results in unbalanced immune responses to dengue; its efficacy is highly variable, and, most significantly, it leads to vaccine-primed exacerbation of disease upon natural infection with dengue.
To develop safe and efficient vaccines, it is important to fully understand the immune response to dengue infections in the population. Dengue and the closely related Zika and Japanese encephalitis viruses belong to the flavivirus family and co-circulate in many areas in the world. Thus, a key question in the field is: How do prior exposures to dengue and flaviviruses contribute to beneficial or harmful immune responses upon subsequent infection with dengue?
Nepal offers a unique opportunity to address this question since dengue, Japanese encephalitis, and potentially Zika virus co-circulate in the country. The goal of this study is to define the impact of previous infections with Japanese encephalitis or Zika on dengue clinical outcomes. Two main components of the immune system help to control an infection: antibodies and T cells. After any viral infection, the immune system keeps a memory of the infection that can be measured via antibodies in the blood. We will obtain blood samples of dengue-confirmed patients from Nepal and determine the relationship between their previous history of infections with Japanese encephalitis, Zika and dengue (as assessed via antibody responses to these viruses) and their dengue disease severity.
Six-Month Project Update
By studying dengue and the related flaviviruses, Japanese Encephalitis (JEV) and Zika (ZIKV), we can develop safer and more effective vaccines and therapies. JEV and the four strains of DENV have very similar structures, and the immune system can target similar sites on these viruses. These similarities make it hard for researchers to detect specific antibody responses to only one flavivirus.
I plan to test two different techniques to determine the most specific and sensitive approach for detection of pre-exposure to JEV. I will test an in-house ELISA and an existing commercial JEV-IgG Kit from InBios. We will compare both approaches using samples collected in 2017.
We accomplished several major goals in the first six months of this project. First, it was critical that we develop procedures to safely manage research and collect samples in Nepal during the pandemic. We also launched new biohazard safety protocols and risk assessments needed to work on JEV in our Biosafety Level 3 facility at LJI.
The next six months will be critical for the project as we define the best approach to determine the JEV immune status of patients, including for patients samples collected in 2021.