Vaccinology

Recent developments in the field of innate and adaptive immunity have taught us a lot on the interplay of innate and adaptive immunity and fine-tuning of the response to a given pathogen. This knowledge now enables a rational approach to vaccine development.

Ways we use knowledge

• To develop an in vitro vaccine evaluation system which enables the elucidation of vaccine mechanisms and which can assist in the selection of promising vaccine candidates for clinical evaluation
• To unravel how vaccine formulation, site of administration and use of adjuvants affect the magnitude and phenotype of the induced immune response and its protective capacity
• To understand how pre-existing immune responses determine the response to vaccination.

Constant antigenic drift (point mutations in the hemagglutinin) and occasional antigenic shift (exchange of the RNA segment encoding hemagglutinin) result in rapid changes of the antigenic make-up of circulating influenza viruses. As a consequence current vaccines which rely predominantly on the induction of antibody responses against the viral hemagglutinin rapidly loose effectiveness. In order to develop vaccines that offer broader protection against drift and shift variants we study vaccines which contain viral proteins other than hemagglutinin alone, like whole inactivated virus vaccines or virosomes with encapsulated or membrane-incorporated conserved viral proteins.

With these vaccines we aim at the induction of influenza-specific cytotoxic T lymphocytes in addition to induction of antibody responses. Moreover, we combine the selected vaccines with suitable adjuvants which can help in further broadening the immune response. This work is performed in the context of the EU-funded consortium UNISEC.

Current influenza vaccines are buffered solutions containing more or less purified virus components. For storage and distribution this formulation requires tightly controlled temperature conditions in order to maintain the antigenic properties of the viral proteins. Moreover, administration is restricted to parenteral injection usually via the intramuscular route.

In collaboration with the Department of Pharmaceutical Biology and Biotechnology of the University of Groningen (Prof. H.W. Frijlink) we develop procedures to formulate influenza vaccines as dry powder making use of sugarglass technology for stabilization of the protein antigens. Using the vaccine powder, alternative administration routes like pulmonary and sublingual delivery are explored