title: A novel vaccine adjuvant comprised of a synthetic innate defence regulator peptide and CpG oligonucleotide links innate and adaptive immunity.
abstract: There has been an increased demand for the development of novel vaccine adjuvants that lead to enhanced induction of protection from infectious challenges and development of immunological memory. A novel vaccine adjuvant was developed comprising a complex containing CpG oligonucleotide and the synthetic cationic innate defence regulator peptide HH2 that has enhanced immune modulating activities. The complex of HH2 and the CpG oligonucleotide 10101 was a potent inducer of cytokine/chemokine expression ex vivo, retained activity following extended storage, had low associated cytotoxicity, and upregulated surface marker expression in dendritic cells, a critical activity for a vaccine adjuvant. Immunization of mice with a coformulation of the HH2-CpG complex and pertussis toxoid significantly enhanced the induction of toxoid-specific antibody titres when compared to toxoid alone, inducing high titres of IgG1 and IgG2a, typical of a balanced Th1/Th2 response, and also led to high IgA titres. This study demonstrates the potential application of the HH2-CpG complex as a vaccine adjuvant.
authors.affiliation: Centre for Microbial Diseases and Immunity Research, University of British Columbia, BC, Canada.
authors.forename: Jason
authors.initials: J
authors.lastname: Kindrachuk
authors.forename: Håvard
authors.initials: H
authors.lastname: Jenssen
authors.forename: Melissa
authors.initials: M
authors.lastname: Elliott
authors.forename: Rebecca
authors.initials: R
authors.lastname: Townsend
authors.forename: Anastasia
authors.initials: A
authors.lastname: Nijnik
authors.forename: Song F
authors.initials: SF
authors.lastname: Lee
authors.forename: Volker
authors.initials: V
authors.lastname: Gerdts
authors.forename: Lorne A
authors.initials: LA
authors.lastname: Babiuk
authors.forename: Scott A
authors.initials: SA
authors.lastname: Halperin
authors.forename: Robert E W
authors.initials: RE
authors.lastname: Hancock
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D000992:Antitoxins / Q000097:blood; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology; D004355:Drug Stability; D005260:Female; D007109:Immunity / Q000187:drug effects*; D007113:Immunity, Innate / Q000187:drug effects*; D007070:Immunoglobulin A / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D051379:Mice; D008807:Mice, Inbred BALB C; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology* / Q000633:toxicity; D010455:Peptides / Q000138:chemical synthesis / Q000494:pharmacology* / Q000633:toxicity; D010567:Pertussis Vaccine / Q000276:immunology; D014121:Toxoids / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000907:Antibodies, Bacterial; D000992:Antitoxins; C523579:CPG 10101; D016207:Cytokines; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D009838:Oligodeoxyribonucleotides; D010455:Peptides; D010567:Pertussis Vaccine; D014121:Toxoids; C051093:pertussis toxoid