Original articles
Jasmine Tomar, Wouter F. Tonnis, Harshad P. Patil, Anne H. de boer, Paul Hagedoorn, Rita Vanbever, Henderik W. Frijlink, Wouter L. J. Hinrichs. Pulmonary immunization: deposition site is of minor relevance for influenza vaccination but deep lung deposition is crucial for hepatitis B vaccination[J]. Acta Pharmaceutica Sinica B, 2019, 9(6): 1231-1240

Pulmonary immunization: deposition site is of minor relevance for influenza vaccination but deep lung deposition is crucial for hepatitis B vaccination
Jasmine Tomara, Wouter F. Tonnisa, Harshad P. Patilb, Anne H. de boera, Paul Hagedoorna, Rita Vanbeverb, Henderik W. Frijlinka, Wouter L. J. Hinrichsa
a Department of Pharmaceutical Technology and Biopharmacy, University of Groningen, Groningen 9713 AV, the Netherlands;
b Advanced Drug Delivery and Biomaterials, Louvain Drug Research Institute (LDRI), Université catholique de Louvain, Brussels 1200, Belgium
Vaccination via the pulmonary route could be an attractive alternative to parenteral administration. Research towards the best site of antigen deposition within the lungs to induce optimal immune responses has conflicting results which might be dependent on the type of vaccine and/or its physical state. Therefore, in this study, we explored whether deep lung deposition is crucial for two different vaccines, i.e., influenza and hepatitis B vaccine. In view of this, influenza subunit vaccine and hepatitis B surface antigen were labeled with a fluorescent dye and then spray-dried. Imaging data showed that after pulmonary administration to mice the powders were deposited in the trachea/central airways when a commercially available insufflator was used while deep lung deposition was achieved when an in-house built aerosol generator was used. Immunogenicity studies revealed that comparable immune responses were induced upon trachea/central airways or deep lung targeting of dry influenza vaccine formulations. However, for hepatitis B vaccine, no immune responses were induced by trachea/central airways deposition whereas they were considerable after deep lung deposition. Thus, we conclude that deep lung targeting is not a critical parameter for the efficacy of pulmonary administered influenza vaccine whereas for hepatitis B vaccine it is.
Key words:    Inhalation    Powders    Deep lung deposition    Influenza    Hepatitis B   
Received: 2019-01-30     Revised: 2019-05-13
DOI: 10.1016/j.apsb.2019.05.003
Funds: This research was funded by the European Union Seventh Framework Program 19 (FP7-2007-2013) and Universal Influenza Vaccines Secured (UNISEC) consortium under grant agreement No. 602012. The authors would like to thank the technicians from the Central Animal Facility for assistance with animal experiments at University of Groningen, The Netherlands. Also, special thanks to Anko Eissens for scanning electron microscope pictures.
Corresponding author: Wouter L. J. Hinrichs     Email:w.l.j.hinrichs@rug.nl
Author description:
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Jasmine Tomar
Wouter F. Tonnis
Harshad P. Patil
Anne H. de boer
Paul Hagedoorn
Rita Vanbever
Henderik W. Frijlink
Wouter L. J. Hinrichs

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