PhD ceremony Mr. H. Patil: Development of adjuvanted influenza vaccines for pulmonary delivery

PhD ceremony: Mr. H. Patil

Dissertation: Development of adjuvanted influenza vaccines for pulmonary delivery

Promotor(s): prof. A.L.W. Huckriede, prof. H.W. Frijlink, prof. J.C. Wilschut

Faculty: Medical Sciences

Influenza virus is well known for its ability to cause seasonal epidemics and occasional pandemics, both with very large impact on society. Vaccination has proven to be effective in controlling influenza epidemics and pandemics but current vaccines are still suboptimal: they have to be administered by tedious intramuscular injection; are highly vulnerable to degradation when not stored within a very tight temperature range (2-8°C), and they fail to elicit immunity in the nose and throat and thus to prevent early stages of the infection.

To overcome these drawbacks we converted liquid vaccine to a dry powder and delivered this powder vaccine directly to the lungs (pulmonary immunization). Dry powder vaccines produced with suitable sugars as stabilizer were stable at temperatures of 30°C for at least 3 months. Two administrations of these powder vaccines to the lungs elicited influenza specific immunity comparable to that achieved by conventional intramuscular injection. The immune responses could be further improved and the local immunity in the airways could be stimulated by including suitable immune-stimulating agents, so-called adjuvants, in the vaccine.

The findings in this thesis indicate that the production of stable influenza vaccines is feasible and that such vaccines elicit strong local and systemic immunity when administered to the lungs e.g. by simple inhalation. The stability of the vaccine and the ease of administration makes dry powder vaccines especially suitable for use in resource-poor countries and for mass vaccination campaigns as required in case of pandemics.