title: Immunogenicity and protective efficacy of neonatal vaccination against Bordetella pertussis in a murine model: evidence for early control of pertussis.
abstract: A significant resurgence of early cases of pertussis is being observed in infants too young to have yet completed their three-dose vaccination schedule. In this study, murine models of immunization and Bordetella pertussis challenge were adapted to early life. This allowed comparative evaluation of immunogenicity and protective efficacy of immunization initiated in the neonatal period (7-day-old mice) or in infancy (3-week-old mice) with diphtheria-tetanus-whole-cell pertussis (DTPw) and diphtheria-tetanus-acellular pertussis (DTPa) vaccines. Neonatal DTPa vaccination induced strong pertussis-specific antibody and memory responses. Patterns of bacterial clearance were similar in both age groups. In contrast, as observed in human neonates, neonatal DTPw priming did not induce significant antibody responses to pertussis toxin (PT) and filamentous hemagglutinin (FHA) and even interfered with subsequent antibody responses. However, this did not reflect induction of permanent neonatal tolerance, as antigen-specific antibodies could be elicited by subsequent exposure to DTPa. Furthermore, despite these blunted PT and FHA antibody responses, the protective efficacy of DTPw in neonatal mice proved similar to that in infant mice, resulting in complete bacterial clearance at day 8 after B. pertussis challenge. Thus, neonatal priming with antipertussis vaccines should be considered to reduce the window of vulnerability to pertussis at the time of its greatest severity.
authors.affiliation: World Health Organization Collaborating Center for Vaccinology and Neonatal Immunology, Department of Pathology and Pediatrics, University of Geneva, Geneva, Switzerland.
authors.forename: Caroline
authors.initials: C
authors.lastname: Roduit
authors.forename: Paola
authors.initials: P
authors.lastname: Bozzotti
authors.forename: Nathalie
authors.initials: N
authors.lastname: Mielcarek
authors.forename: Paul-Henri
authors.initials: PH
authors.lastname: Lambert
authors.forename: Giuseppe
authors.initials: G
authors.lastname: del Giudice
authors.forename: Camille
authors.initials: C
authors.lastname: Locht
authors.forename: Claire-Anne
authors.initials: CA
authors.lastname: Siegrist
mesh_terms: D018829:Adhesins, Bacterial / Q000276:immunology; D000818:Animals; D000831:Animals, Newborn; D000907:Antibodies, Bacterial / Q000096:biosynthesis / Q000276:immunology; D000942:Antigens, Bacterial / Q000276:immunology; D001886:Bordetella pertussis / Q000276:immunology*; D015721:Diphtheria-Tetanus-Pertussis Vaccine / Q000276:immunology*; D022681:Diphtheria-Tetanus-acellular Pertussis Vaccines / Q000276:immunology*; D004195:Disease Models, Animal; D006388:Hemagglutinins / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D037342:Pertussis Toxin; D014611:Vaccination; D010566:Virulence Factors, Bordetella / Q000276:immunology; D014917:Whooping Cough / Q000517:prevention & control*
chemical_list: D018829:Adhesins, Bacterial; D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D015721:Diphtheria-Tetanus-Pertussis Vaccine; D022681:Diphtheria-Tetanus-acellular Pertussis Vaccines; D006388:Hemagglutinins; D010566:Virulence Factors, Bordetella; C065273:filamentous hemagglutinin adhesin, Bordetella pertussis; D037342:Pertussis Toxin