title: A New Vaccine Delivery Vehicle and Adjuvant Candidate: Bordetella pertussis Inactivated Whole Cells Entrapped in Alginate Microspheres.
abstract: There is no doubt about the whole cell pertussis vaccine efficacy, but it is necessary to improve the vaccine quality specially to decrease its toxicity by obtaining good immunogenicity with low bacterial content. In this work, under optimum condition inactivated B. pertussis bacteria cells entrapped with alginate microparticles were fabricated and in vivo immunogenicity and ptency of new microparticle based vaccine were evaluated in mice. Microspheres loaded with inactive B. pertussis bacterium cells were prepared via an emulsification method and analyzed for morphology, size, polydispersity index, loading efficiency, loading capacity, release profile and in vivo potency. The inactivated bacterial suspension mixture prepared in this work was nontoxic and showed potent ED50 (1:333 of human dose) and preserved agglutinins 1, 2, 3. The optimum conditions for the preparation of microparticles were achieved at alginate concentration 3.8% (w/v), CaCl2 8% (w/v), PLL 0.1% (w/v), lipophilic surfactant 0.22 (%w/v), hydrophilic surfactant 3.6 (%w/v), cross linking time 3min, homogenization rate 600 rpm, and alginate to CaCl2 solution ratio 4. Both empty and B. pertussis loaded microparticles exhibited smooth surface texture and relatively spherical shape. The B. pertussis encapsulated microspheres fabricated under optimized conditions showed mean particle size 151.1 μm, polydispersity index 0.43, loading efficiency 89.6%, loading capacity 36.3%, and relatively constant release rate lasted to 15 days. In vivo immunogenicity and protection study against wild type challenge showed strongly higher potency (approximately 2.5 fold) of encapsulated B. pertussis organisms than non-encapsulated conventional aluminum hydroxide adsorbed vaccine. It can be concluded that microencapsulation of inactive B. pertussis cells appears to be a suitable approach for improving the wP vaccine quality, specially by obtaining good immunogenicity with low bacterial content.
authors.affiliation: Department of Microbiology, Pasteur Institute of Iran, Tehran, Iran.
authors.forename: Naser Mohammadpour
authors.initials: NM
authors.lastname: Dounighi
authors.affiliation: Departments of Microbiology and Mycology, Pasteur Institute of Iran, P. O. Box 13164, Tehran, Iran.
authors.forename: Fereshteh
authors.initials: F
authors.lastname: Shahcheraghi
authors.affiliation: Departments of Microbiology and Mycology, Pasteur Institute of Iran, P. O. Box 13164, Tehran, Iran.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Razzaghi-Abyaneh
authors.affiliation: Department of Human Vaccine and Serum, Razi Vaccine and Serum Research Institute, Agricultural Research, Education and Extension Organization, Karaj, Iran.
authors.forename: Mojtaba
authors.initials: M
authors.lastname: Nofeli
authors.affiliation: Department of Human Vaccine and Serum, Razi Vaccine and Serum Research Institute, Agricultural Research, Education and Extension Organization, Karaj, Iran.
authors.forename: Hossein
authors.initials: H
authors.lastname: Zolfagharian
mesh_terms: D000464:Alginates / Q000008:administration & dosage*; D000818:Animals; D001886:Bordetella pertussis / Q000166:cytology / Q000276:immunology; D004339:Drug Compounding / Q000379:methods; D016503:Drug Delivery Systems / Q000379:methods*; D020723:Glucuronic Acid / Q000008:administration & dosage / Q000276:immunology; D006603:Hexuronic Acids / Q000008:administration & dosage / Q000276:immunology; D051379:Mice; D008863:Microspheres; D010316:Particle Size; D010567:Pertussis Vaccine / Q000008:administration & dosage* / Q000276:immunology
chemical_list: D000464:Alginates; D006603:Hexuronic Acids; D010567:Pertussis Vaccine; D020723:Glucuronic Acid
keywords: Bordetella pertussis; bacteria; immunogenicity; microparticle; potency; whole cell vaccine