A virosomal respiratory syncytial virus vaccine candidate with a Toll-like receptor ligand as built-in adjuvant. Preclinical evaluation of immunogenicity, efficacy and safety

PhD ceremony: Mr. T. Kamphuis, 11.00 uur, Academiegebouw, Broerstraat 5, Groningen

Dissertation: A virosomal respiratory syncytial virus vaccine candidate with a Toll-like receptor ligand as built-in adjuvant. Preclinical evaluation of immunogenicity, efficacy and safety

Promotor(s): prof. J.C. Wilschut

Faculty: Medical Sciences

Respiratory syncytial virus (RSV) is the major cause of lower respiratory tract infection in infants and young children. Infection with RSV also causes significant morbidity and mortality in elderly people. A vaccine against RSV would significantly reduce the health burden caused by RSV infection.

In this study, we evaluated a virosomal RSV vaccine. A virosome is a virus particle without the genetic material. It does contain the surface proteins causing the immune response after vaccination. A virosome therefore is similar to a virus particle for the immune system, but is incapable of replication and therefore cannot cause disease. To improve the immune response induced by the virosomes, we included a so-called TLR ligand in the virosomal structure. Inclusion of this TLR ligand stimulates and skews the immune response. It has a positive influence on both safety and efficacy of the vaccine. In this study, we showed that is it feasible to produce RSV virosomes with a built-in TLR ligand. We subsequently tested this vaccine candidate in animal models. These tests showed the vaccine to be immunogenic and safe when administered to animals. Vaccinated animals were protected against infection with live virus.