Annie Elong Ngono, Ph.D.

How does prior exposure to closely-related viruses contribute to protection or disease during subsequent infection with a related virus?

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.

SPARKing Impact: Results obtained from this study will set a critical framework for our future investigation of the quality and the quantity of the T cell responses that modulate clinical disease manifestations in dengue patients. Importantly, they will inform development of safe and effective vaccines and therapies against not only dengue virus but also other globally relevant pathogens, including coronaviruses.