title: Novel vaccine formulations against pertussis offer earlier onset of immunity and provide protection in the presence of maternal antibodies.
abstract: Whooping cough is a respiratory illness most severe in infants and young children. While the introduction of whole-cell (wP) and acellular pertussis (aP) vaccines has greatly reduced the burden of the disease, pertussis remains a problem in neonates and adolescents. New vaccines are needed that can provide early life and long-lasting protection of infants. Vaccination at an early age, however, is problematic due to the interference with maternally derived antibodies (MatAbs) and the bias towards Th2-type responses following vaccination. Here we report the development of a novel vaccine formulation against pertussis that is highly protective in the presence of MatAbs. We co-formulated pertussis toxoid (PTd) and filamentous hemagglutinin (FHA) with cytosine-phosphate-guanosine oligodeoxynucleotides (CpG ODN), cationic innate defense regulator (IDR) peptide and polyphosphazene (PP) into microparticle and soluble vaccine formulations and tested them in murine and porcine models in the presence and absence of passive immunity. Vaccines composed of the new adjuvant formulations induced an earlier onset of immunity, higher anti-pertussis IgG2a and IgA titers, and a balanced Th1/Th2-type responses when compared to immunization with Quadracel(®), one of the commercially available vaccines for pertussis. Most importantly, the vaccines offered protection against challenge infection in the presence of passively transferred MatAbs.
authors.affiliation: Vaccine and Infectious Disease Organization (VIDO), University of Saskatchewan S7N 5E3, SK, Canada.
authors.forename: Monika
authors.initials: M
authors.lastname: Polewicz
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Gracia
authors.forename: Srinivas
authors.initials: S
authors.lastname: Garlapati
authors.forename: Jill
authors.initials: J
authors.lastname: van Kessel
authors.forename: Stacy
authors.initials: S
authors.lastname: Strom
authors.forename: Scott A
authors.initials: SA
authors.lastname: Halperin
authors.forename: Robert E W
authors.initials: RE
authors.lastname: Hancock
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: D018829:Adhesins, Bacterial / Q000276:immunology*; D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood / Q000276:immunology*; D058491:Bacterial Load; D005260:Female; D006388:Hemagglutinins / Q000276:immunology; D007112:Immunity, Maternally-Acquired; D007070:Immunoglobulin A / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D051379:Mice; D008807:Mice, Inbred BALB C; D009838:Oligodeoxyribonucleotides; D010567:Pertussis Vaccine / Q000276:immunology* / Q000627:therapeutic use; D013552:Swine; D058408:Th1-Th2 Balance; D014121:Toxoids / Q000276:immunology*; D010566:Virulence Factors, Bordetella / Q000276:immunology*; D014917:Whooping Cough / Q000276:immunology / Q000517:prevention & control*
chemical_list: D018829:Adhesins, Bacterial; D000276:Adjuvants, Immunologic; D000907:Antibodies, Bacterial; D006388:Hemagglutinins; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D009838:Oligodeoxyribonucleotides; D010567:Pertussis Vaccine; D014121:Toxoids; D010566:Virulence Factors, Bordetella; C065273:filamentous hemagglutinin adhesin, Bordetella pertussis; C051093:pertussis toxoid