title: Immunization with PCEP microparticles containing pertussis toxoid, CpG ODN and a synthetic innate defense regulator peptide induces protective immunity against pertussis.
abstract: We investigated the efficacy of a novel microparticle (MP) based vaccine formulation consisting of pertussis toxoid (PTd), polyphosphazene (PCEP), CpG ODN 10101 and synthetic cationic innate defense regulator peptide 1002 (IDR) against Bordetella pertussis in mice. We studied whether encapsulation of these IDR-CpG ODN complexes into polyphosphazene-based microparticles further enhanced their immunomodulatory activity compared to soluble formulations containing PCEP (SOL), or without PCEP (AQ). In vitro stimulation of murine macrophages showed MP induced significantly higher levels of pro-inflammatory cytokines. When assessed in a B. pertussis infection challenge model, a single immunization with MP formulation led to significantly lower bacterial loads compared to other formulations and non-vaccinated animals. ELISPOT of splenocytes showed that MP group mice had significantly higher number of antigen-specific IL-17 secreting cells. The cytokine profile in lung homogenates of MP group mice after challenge showed significantly higher amounts of MCP-1, TNF-α, IFN-γ, IL-12 and IL-17 and significantly lowered IL-10 levels suggesting a strong Th1 shift. Protection was observed against challenge infection with B. pertussis. On the other hand protective immune responses elicited in Quadracel(®) immunized mice were Th2 skewed. Hence, we conclude that formulation of PTd, PCEP, CpG ODN and IDR into MP generates a protective immune response in mice against pertussis emphasizing the potential of MP as a delivery vehicle for the potential development of single-shot vaccines.
authors.affiliation: Vaccine and Infectious Disease Organization/International Vaccine Center, University of Saskatchewan, 120 Veterinary Road, Saskatoon, SK, S7N 5E3, Canada.
authors.forename: Srinivas
authors.initials: S
authors.lastname: Garlapati
authors.forename: Nelson F
authors.initials: NF
authors.lastname: Eng
authors.forename: Tadele G
authors.initials: TG
authors.lastname: Kiros
authors.forename: Jason
authors.initials: J
authors.lastname: Kindrachuk
authors.forename: George K
authors.initials: GK
authors.lastname: Mutwiri
authors.forename: Robert E W
authors.initials: RE
authors.lastname: Hancock
authors.forename: Scott A
authors.initials: SA
authors.lastname: Halperin
authors.forename: Andrew A
authors.initials: AA
authors.lastname: Potter
authors.forename: Lorne A
authors.initials: LA
authors.lastname: Babiuk
authors.forename: Volker
authors.initials: V
authors.lastname: Gerdts
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000008:administration & dosage*; D058491:Bacterial Load; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004337:Drug Carriers / Q000008:administration & dosage*; D005260:Female; D008168:Lung / Q000382:microbiology; D008214:Lymphocytes / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008863:Microspheres; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage*; D010567:Pertussis Vaccine / Q000008:administration & dosage / Q000276:immunology*; D010666:Phenylpropionates / Q000008:administration & dosage*; D011108:Polymers / Q000008:administration & dosage*; D012376:Rodent Diseases / Q000517:prevention & control; D013154:Spleen / Q000276:immunology; D014121:Toxoids / Q000008:administration & dosage*; D014917:Whooping Cough / Q000517:prevention & control*
chemical_list: D000276:Adjuvants, Immunologic; D023181:Antimicrobial Cationic Peptides; C408982:CPG-oligonucleotide; D016207:Cytokines; D004337:Drug Carriers; C549067:IDR 1002; D009838:Oligodeoxyribonucleotides; D010567:Pertussis Vaccine; D010666:Phenylpropionates; D011108:Polymers; D014121:Toxoids; C051093:pertussis toxoid; C508285:poly(bis(carboxylatoethylphenoxy)phosphazene)