Development of a thermostable spray dried outer membrane vesicle pertussis vaccine for pulmonary immunization

J Control Release. 2018 Sep 28:286:167-178. doi: 10.1016/j.jconrel.2018.07.035. Epub 2018 Jul 24.

Abstract

Worldwide resurgence of whooping cough calls for improved, next-generation pertussis vaccines that induce broad and long-lasting immunity. A mucosal pertussis vaccine based on outer membrane vesicles (omvPV) is a promising candidate. Further, a vaccine that is stable outside the cold chain would be of substantial advantage for worldwide distribution and application. A vaccine formulated as a powder could both stabilize the vaccine as well as make it suitable for pulmonary vaccination. To that end, we developed a spray dried omvPV with improved stability compared to the liquid omvPV formulation. Spray drying did not affect the structural integrity of the omvPV. The antigenicity of Vag8, a major antigen in omvPV was diminished slightly and an altered tryptophan fluorescence indicated some changes in protein structure. However, when administered via the pulmonary route in mice after reconstitution, spray dried omvPV showed comparable immune responses and protection against challenge with live B. pertussis as liquid omvPV. Mucosal IgA and Th17 responses were established in addition to broad systemic IgG and Th1/Th17 responses, indicating the induction of an effective immunity profile. Overall, a spray dried omvPV was developed that maintained effective immunogenic properties and has an improved storage stability.

Keywords: Outer membrane vesicles; Pertussis vaccine; Spray drying and pulmonary administration.Sss.

MeSH terms

  • Animals
  • Antigens, Bacterial / administration & dosage*
  • Antigens, Bacterial / chemistry
  • Antigens, Bacterial / immunology
  • Antigens, Bacterial / therapeutic use
  • Bordetella pertussis / chemistry
  • Bordetella pertussis / immunology*
  • Desiccation
  • Drug Administration Routes
  • Drug Stability
  • Female
  • Hot Temperature
  • Lung / immunology
  • Mice, Inbred BALB C
  • Particle Size
  • Pertussis Vaccine / administration & dosage*
  • Pertussis Vaccine / chemistry
  • Pertussis Vaccine / immunology
  • Pertussis Vaccine / therapeutic use
  • Powders
  • Th1 Cells / immunology
  • Th17 Cells / immunology
  • Vaccination
  • Whooping Cough / immunology
  • Whooping Cough / prevention & control*

Substances

  • Antigens, Bacterial
  • Pertussis Vaccine
  • Powders