Human parainfluenza viruses (hPIV) are a very important cause of paediatric hospitalization due to
acute respiratory tract infections. There are no vaccines or hPIV-targeting therapeutics available to
prevent or treat disease caused by these globally circulating respiratory viruses. The aim of this
research proposal is to develop antivirals against hPIV1 and -3, the two most important hPIV types.
These new antivirals will be based on single-domain antibodies (also known as Nanobodies®),
which are derived from heavy-chain-only antibodies that are found in mammals classified in the
camel family (llama, alpaca, camel,…). Our aim is to isolate and characterize single-domain
antibodies with very strong hPIV-neutralizing activity. Hereto we will immunize a llama with hPIV
and use recombinant DNA technology to isolate single-domain antibodies that can potently
neutralize hPIV in vitro and in vivo. We will also study in molecular detail how these antibodies
inhibit hPIV infection and determine the crystal structure of prefusion F using prefusion F-specific
single-domain antibodies. In a second part of the project, we aim at developing a new method for
delivering single-domain antibody-based drugs to the upper respiratory tract in a safe, economical
and practical way. Hereto, we will genetically modify bacteria that naturally reside in this
environment in such a way that they secrete biologically active single-domain antibodies.