Pulmonary delivery of influenza vaccine formulations in cotton rats: site of deposition plays a minor role in the protective efficacy against clinical isolate of H1N1pdm virus

Abstract

Administration of influenza vaccines to the lungs could be an attractive alternative to conventional parenteral administration. In this study, we investigated the deposition site of pulmonary delivered liquid and powder influenza vaccine formulations and its relation to their immunogenicity and protective efficacy. In vivo deposition studies in cotton rats revealed that, the powder formulation was mainly deposited in the trachea ( ∼ 65%) whereas the liquid was homogenously distributed throughout the lungs ( ∼ 96%). In addition, only 60% of the antigen in the powder formulation was deposited in the respiratory tract with respect to the liquid formulation. Immunogenicity studies showed that pulmonary delivered liquid and powder influenza formulations induced robust systemic and mucosal immune responses (significantly higher by liquids than by powders). When challenged with a clinical isolate of homologous H1N1pdm virus, all animals pulmonary administered with placebo had detectable virus in their lungs one day post challenge. In contrast, none of the vaccinated animals had detectable lung virus titers, except for two out of eight animals from the powder immunized group. Also, pulmonary vaccinated animals showed no or little signs of infection like increase in breathing frequency or weight loss upon challenge as compared to animals from the negative control group. In conclusion, immune responses induced by liquid formulation were significantly higher than responses induced by powder formulation, but the overall protective efficacy of both formulations was comparable. Thus, pulmonary immunization is capable of inducing protective immunity and the site of antigen deposition seems to be of minor relevance in inducing protection.

Keywords:

• Whole inactivated influenza virus vaccine
• inhalation
• deposition
• immunogenicity
• protection

Acknowledgements

The authors would like to thank the National Institute for Biological Standards and Control (NIBSC) for kindly providing NIBRG-121 virus; Prof. Hubert Niesters, UMCG, The Netherlands, for providing A/California/2009 (E9-6714) virus, and Anko Eissens for help with SEM. Further, we would also like to thank Hette Faber, UMCG, The Netherlands, for the plethysmography apparatus for the BF measurement and the central animal facility of the UMCG for animal caretaking and help with vaccinations

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

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.