Evaluation of Monophosphoryl Lipid A as Adjuvant for Pulmonary Delivered Influenza Vaccine

J Control Release. 2014 Jan 28;174:51-62. doi: 10.1016/j.jconrel.2013.11.013. Epub 2013 Nov 21.

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.

Keywords: IgA; Inhalation; Protection; Spray-freeze-drying; Whole inactivated virus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / administration & dosage*
  • Adjuvants, Immunologic / chemistry
  • Administration, Inhalation
  • Animals
  • Antibodies, Viral / blood
  • Antibodies, Viral / immunology
  • Bronchoalveolar Lavage Fluid / immunology
  • Dogs
  • Female
  • Hemagglutination Tests
  • Immunoglobulin A / immunology
  • Immunoglobulin G / blood
  • Immunoglobulin G / immunology
  • Influenza A Virus, H1N1 Subtype / immunology
  • Influenza A Virus, H3N2 Subtype / immunology
  • Influenza Vaccines / administration & dosage*
  • Influenza Vaccines / chemistry
  • Interferon-gamma / immunology
  • Lipid A / administration & dosage
  • Lipid A / analogs & derivatives*
  • Lipid A / chemistry
  • Lung / immunology
  • Lung / virology
  • Madin Darby Canine Kidney Cells
  • Mice
  • Mice, Inbred BALB C
  • Nasal Mucosa / immunology

Substances

  • Adjuvants, Immunologic
  • Antibodies, Viral
  • Immunoglobulin A
  • Immunoglobulin G
  • Influenza Vaccines
  • Lipid A
  • Interferon-gamma
  • monophosphoryl lipid A