Evaluation of monophosphoryl lipid A as adjuvant for pulmonary delivered influenza vaccine

Harshad P. Patil, Senthil Murugappan, Wouter Ter Veer, Tjarko Meijerhof, Aalzen De Haan, Henderik W. Frijlink, Jan Wilschut, Wouter L.J. Hinrichs, Anke Huckriede*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Prophylaxis against influenza could be improved by the development of a stable, easy to deliver, potent mucosal vaccine. In this study, we spray-freeze-dried (SFD) whole inactivated virus influenza vaccine (WIV) alone or supplemented with monophosphoryl lipid A (MPLA) using inulin as a lyoprotectant. Physical characterization revealed that the SFD powder consisted of highly porous particles with a size distribution suitable for pulmonary administration. The receptor-binding properties of WIV and the immunostimulatory properties of MPLA were preserved after spray-freeze-drying as indicated by unchanged hemagglutination titers and a retained ability of the vaccine to activate NFkB after incubation with a reporter cell line, respectively. Pulmonary vaccination of mice with MPLA-adjuvanted liquid or powder WIV resulted in induction of higher mucosal and systemic antibody concentrations than vaccination with non-adjuvanted formulations. When exposed to influenza virus, mice immunized with MPLA-adjuvanted pulmonary vaccine showed similar protection in terms of reduction in lung virus titers and prevention ofweight loss as mice immunized intramuscularly with subunit vaccine. Characterization of the antibody response revealed a balanced IgG2a-to-IgG1 profile along with induction of both memory IgA- and IgG-producing B cells in mice immunized with MPLA-adjuvanted vaccine. These studies suggest that themucosal and systemic immune responses to pulmonary delivered influenza vaccines can be significantly enhanced by using MPLA as adjuvant. MPLA-adjuvanted SFD vaccine was particularly effective implying that delivery of adjuvanted vaccine powder to the lungs can be an attractive way of immunization against influenza. (C) 2013 Elsevier B.V. All rights reserved.

Original languageEnglish
Pages (from-to)51-62
Number of pages12
JournalJournal of controlled release : official journal of the Controlled Release Society
Issue number1
Publication statusPublished - 28-Jan-2014


  • IgA
  • Inhalation
  • Protection
  • Spray-freeze-drying
  • Whole inactivated virus
  • immunoglobulin A
  • immunoglobulin G1
  • immunoglobulin G2a
  • immunological adjuvant
  • influenza vaccine
  • inulin
  • phosphoryl lipid A
  • subunit vaccine
  • aerosol
  • animal experiment
  • animal model
  • animal tissue
  • antibody blood level
  • antibody response
  • article
  • B lymphocyte
  • controlled study
  • drug formulation
  • evaluation study
  • female
  • freeze drying
  • hemagglutination
  • hemagglutination inhibition
  • humoral immunity
  • immunoglobulin production
  • Influenza virus
  • liquid
  • mouse
  • mucosal immunity
  • nonhuman
  • particle size
  • powder
  • priority journal
  • receptor binding
  • vaccination
  • virus inactivation
  • virus titration
  • weight reduction

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