title: Evaluation of monophosphoryl lipid A as adjuvant for pulmonary delivered influenza vaccine.
abstract: 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 of weight 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 the mucosal 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.
authors.affiliation: Department of Medical Microbiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Harshad P
authors.initials: HP
authors.lastname: Patil
authors.affiliation: Department of Pharmaceutical Technology and Biopharmacy, University of Groningen, Groningen, The Netherlands.
authors.forename: Senthil
authors.initials: S
authors.lastname: Murugappan
authors.affiliation: Department of Medical Microbiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Wouter
authors.initials: W
authors.lastname: ter Veer
authors.affiliation: Department of Medical Microbiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Tjarko
authors.initials: T
authors.lastname: Meijerhof
authors.affiliation: Department of Medical Microbiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Aalzen
authors.initials: A
authors.lastname: de Haan
authors.affiliation: Department of Pharmaceutical Technology and Biopharmacy, University of Groningen, Groningen, The Netherlands.
authors.forename: Henderik W
authors.initials: HW
authors.lastname: Frijlink
authors.affiliation: Department of Medical Microbiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Jan
authors.initials: J
authors.lastname: Wilschut
authors.affiliation: Department of Pharmaceutical Technology and Biopharmacy, University of Groningen, Groningen, The Netherlands.
authors.forename: Wouter L J
authors.initials: WL
authors.lastname: Hinrichs
authors.affiliation: Department of Medical Microbiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. Electronic address: a.l.w.huckriede@umcg.nl.
authors.forename: Anke
authors.initials: A
authors.lastname: Huckriede
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000737:chemistry; D000280:Administration, Inhalation; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D004285:Dogs; D005260:Female; D006386:Hemagglutination Tests; D007070:Immunoglobulin A / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology; D053122:Influenza A Virus, H3N2 Subtype / Q000276:immunology; D007252:Influenza Vaccines / Q000008:administration & dosage* / Q000737:chemistry; D007371:Interferon-gamma / Q000276:immunology; D008050:Lipid A / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry; D008168:Lung / Q000276:immunology / Q000821:virology; D061985:Madin Darby Canine Kidney Cells; D051379:Mice; D008807:Mice, Inbred BALB C; D009297:Nasal Mucosa / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007252:Influenza Vaccines; D008050:Lipid A; D007371:Interferon-gamma; C048436:monophosphoryl lipid A
keywords: IgA; Inhalation; Protection; Spray-freeze-drying; Whole inactivated virus