PhD ceremony Mr. M. Shafique: Development of a mucosal vaccine against Respiratory Syncytial Virus infection

PhD ceremony: Mr. M. Shafique, 11.00 uur, Academiegebouw, Broerstraat 5, Groningen

Dissertation: Development of a mucosal vaccine against Respiratory Syncytial Virus infection

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

Faculty: Medical Sciences

Respiratory syncytial virus (RSV) infection is an important cause of severe respiratory disease in infants and children worldwide, and also forms a serious threat in the elderly. Vaccination against RSV could reduce the burden of RSV infection, but a vaccine is not yet available. In this thesis, the efficacy and safety of a candidate mucosal RSV vaccine was explored. Reconstituted RSV virus membranes (virosomes) were used as a vaccine platform and their capacity to induce protective immune responses was evaluated after intranasal administration in animal studies. Furthermore, the capacity of Toll-like receptor (TLR) ligands and NOD2 ligands to potentiate the induction of safe and effective immune responses was evaluated. The study shows that TLR- and NOD2- ligands, incorporated in RSV virosomal membranes, boosted serum IgG and local IgA antibody responses in the respiratory tract. Immunization with virosomal RSV vaccine, containing TLR/NOD2 ligands, did not prime for enhanced respiratory disease upon challenge of the immunized animals with live virus. Furthermore, the animals were protected from infection. Incorporation of monophosphoryl lipid A, a TLR adjuvant licensed for use in human vaccines, also potentiated the capacity of RSV virosomes to induce protective antibody responses in animals, even in those with an aged immune system. Intranasal administration of RSV virosomes with built-in TLR ligands, therefore, represents a promising approach for vaccination against RSV.