Research in the area of vaccinology development is focused on influenza virus and respiratory syncytial virus (RSV) and aims at the rational design of novel vaccine modalities and formulations. In-depth knowledge of the relevant correlates of immune protection is integrated with recent insights in immunology, in particular in mechanisms of innate immunology, to generate vaccines which are optimally suited to induce effective immune responses.
In the area of influenza virus vaccines, we follow three main research lines.
- Systems immunology techniques are employed to find leads for the development of highly effective influenza vaccines capable of overcoming age- or condition-related impairments of the immune system and suitable for low dose immunization in case of a pandemic.
- For the generation of universal influenza vaccines we re-evaluate old and design new vaccine formulations containing conserved virus antigens to evoke broadly reactive humoral and cellular immune responses.
- In collaboration with our colleagues from the Department of Pharmacy (University of Groningen) we work on stabilization of influenza vaccines to increase vaccine shelf life and to enable vaccine administration via new effective and patient-friendly ways like inhalation.
Systems immunology for improved influenza vaccines
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. We employ this knowledge 1) 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; 2) 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; and 3) to understand how pre-existing immune responses determine the response to vaccination.
Development of cross-reactive influenza vaccines
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.
Stabilized influenza vaccine formulations for mucosal delivery
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