Intranasal immunization with aluminum salt-adjuvanted dry powder vaccine

J Control Release. 2018 Dec 28:292:111-118. doi: 10.1016/j.jconrel.2018.10.020. Epub 2018 Oct 16.

Abstract

Intranasal vaccination using dry powder vaccine formulation represents an attractive, non-invasive vaccination modality with better storage stability and added protection at the mucosal surfaces. Herein we report that it is feasible to induce specific mucosal and systemic antibody responses by intranasal immunization with a dry powder vaccine adjuvanted with an insoluble aluminum salt. The dry powder vaccine was prepared by thin-film freeze-drying of a model antigen, ovalbumin, adsorbed on aluminum (oxy)hydroxide as an adjuvant. Special emphasis was placed on the characterization of the dry powder vaccine formulation that can be realistically used in humans by a nasal dry powder delivery device. The vaccine powder was found to have "passable" to "good" flow properties, and the vaccine was uniformly distributed in the dry powder. An in vitro nasal deposition study using nasal casts of adult humans showed that around 90% of the powder was deposited in the nasal cavity. Intranasal immunization of rats with the dry powder vaccine elicited a specific serum antibody response as well as specific IgA responses in the nose and lung secretions of the rats. This study demonstrates the generation of systemic and mucosal immune responses by intranasal immunization using a dry powder vaccine adjuvanted with an aluminum salt.

Keywords: Aluminum salts; Dry powder; Intranasal; Mucosal immunity; Powder characterization; Vaccine.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / administration & dosage*
  • Adjuvants, Immunologic / chemistry
  • Adjuvants, Immunologic / pharmacokinetics
  • Administration, Intranasal
  • Aluminum Hydroxide / administration & dosage*
  • Aluminum Hydroxide / chemistry
  • Aluminum Hydroxide / pharmacokinetics
  • Aluminum Oxide / administration & dosage*
  • Aluminum Oxide / chemistry
  • Aluminum Oxide / pharmacokinetics
  • Animals
  • Antigens / administration & dosage
  • Antigens / chemistry
  • Antigens / immunology
  • Brain / metabolism
  • Bronchoalveolar Lavage Fluid / immunology
  • Female
  • Immunization
  • Immunoglobulin A / immunology
  • Immunoglobulin G / blood
  • Nasal Lavage Fluid / immunology
  • Ovalbumin / administration & dosage
  • Ovalbumin / chemistry
  • Ovalbumin / immunology
  • Powders
  • Rats, Sprague-Dawley
  • Vaccines / administration & dosage*
  • Vaccines / chemistry
  • Vaccines / pharmacokinetics

Substances

  • Adjuvants, Immunologic
  • Antigens
  • Immunoglobulin A
  • Immunoglobulin G
  • Powders
  • Vaccines
  • Aluminum Hydroxide
  • aluminum oxide hydroxide
  • Ovalbumin
  • Aluminum Oxide