Uncovering the Potential for Dengue Virus Escape from Vaccine-Induced Immunity
Dengue is a serious disease spread by mosquitoes that poses a threat to children’s health, mostly in (sub-)tropical parts of the world. Dengue virus consists of four different types that each can infect a human, with each new infection potentially being more dangerous than the last. Vaccines have been developed to protect children against dengue, but not all vaccines were able to provide sufficient protection, particularly in children who never had dengue before. The immune system of these children was not strong enough and infection with dengue after receiving the vaccination resulted in an increased risk for more serious disease.
A new and improved dengue vaccine that recently became available is now being administered to children regardless of whether they have previously had dengue. However, one concern with the use of this vaccine is the potential for dengue virus to develop vaccine escape. This means that the virus can change to allow it to avoid the immune response triggered by the vaccine, meaning that someone who got vaccinated can still get ill.
In this project, we will study the potential for dengue virus to change and escape from the immune response triggered by the vaccine. To study this, we will create all possible individual variants of the dengue virus envelope protein, the part of the virus that is recognized by the immune system, and test whether any of these variants can escape from protection induced by the vaccine. We will expose this pool of dengue virus variants to human serum, the liquid component of blood, from vaccinated individuals who had or have not had dengue before, and see if any variants are able to survive exposure to antibodies that are present in the serum. We will also investigate which dengue variants are most common under natural conditions, by testing which dengue variants are able to survive in human and mosquito cells in the laboratory and by identifying which variants currently circulate in the field. Our research is critical to make informed decisions about the use of dengue vaccines and for developing better vaccines that keep children safe.