Abstract
Several RSV vaccine candidates, usually based on a recombinant form of the fusion (F) protein that is locked in the prefusion state, are in advanced stage of clinical development. These vaccines target the elderly and pregnant women despite the fact that the need may be greatest in children. It seems that for RSV, the prefusion F protein does not result in sufficient protective RSV immunity in children and adults, and that a correlate of protection (CoP) in children might be different than in adults. Determining a CoP for children turns out to be very challenging and many inconsistent results have been found. In this project, a comprehensive study will be done to map the antibody repertoire of pregnant women, newborns and young children up to 16 months, a.o. using an extensive panel of RSV F specific monoclonal antibodies. Subsequently, differences in the processing of the RSV F protein in primary epithelial cells of children and adults will be investigated by characterizing the virus in WD-PNECs, focusing on the structure of the F protein and the presence of different epitopes. Antibody repertoires and virus characteristics will be correlated with the onset and severity of RSV infection in children. Finally, monoclonal antibodies will be developed using subtractive immunization to target epitopes that correlate with a protective CoP in children. This will support the ultimate goal to find a CoP in children and will help to accelerate vaccine development in children.
Researcher(s)
Research team(s)
Project type(s)