Respiratory Syncytial Virus research
Infections with human respiratory syncytial viruses (hRSV) are very common. The virus circulates every winter season, and normally induces a mild "common cold-like" upper respiratory tract infection. However, in young infants hRSV infections can result in severe respiratory disease, associated with pneumonia and bronchiolitis. This is most often observed during the first year of life, leading to the hospitalisation of up to 2% of all children. In addition to infants, hRSV infections can also cause severe respiratory disease in immunosuppressed adults and the elderly. Finally, hRSV infections have also been associated with the development of asthma and allergy.
No licensed hRSV vaccines are currently available. RSV vaccine development has been hampered by vaccination trials in the 1960's demonstrating that formalin-inactivated (FI) RSV predisposes for enhanced disease following subsequent hRSV infection. Vaccination / challenge studies in rodents suggested that FI-RSV vaccination induces an aberrant or incomplete type of immunity, leading to immunopathology following challenge infection. An additional complicating factor in vaccine development is that also natural hRSV infections do not induce full protective immunity: re-infections continue to occur frequently. Vaccine candidates currently being evaluated in human clinical trials are either live attenuated vaccines, recombinant vector vaccines or subunit vaccines.
At the department of Virology, RSV research has mainly focussed on the characterisation of the (immuno)pathogenesis of RSV infections in children. Samples were collected from infants with clinically moderate or severe hRSV infections during the acute and convalescent stages, and the specific humoral and cellular immune responses were studied in detail. A non-human primate model for hRSV infections was developed to study vaccine-related immunopathogenesis. Finally, the department was also involved in Phase I/II and Phase III clinical trials of a subunit hRSV vaccine produced by a French company. This work has resulted in two PhD theses, by Afke Brandenburg (“Respiratory Syncytial Virus Infections in Infants. Determinants of Clinical Severity”, Rotterdam 2000) and Leon de Waal Respiratory Syncytial Virus. Anti-viral immunity in humans and macaques, Rotterdam 2003).
- Involvement of immunopathology in normal hRSV disease severity
- Involvement of hRSV infections in development of asthma and allergy
- Characterisation of the immune response to hRSV infection
- Macaque model of hRSV-related immunopathology