title: Impaired long-term maintenance and function of Bordetella pertussis specific B cell memory.
abstract: Frequent occurrence of whooping cough in vaccinated populations suggests limited duration of vaccine-induced immunological memory. To investigate peculiarities in B cell memory specific for pertussis antigens P.69 pertactin (P.69 Prn), pertussis toxin (Ptx) and filamentous hemagglutinin (FHA), we monitored the induction and maintenance of specific serum IgG, long-lived bone marrow (BM)-derived plasma cell (PC) and splenic memory B cell (B(mem)) populations in a long-term preclinical vaccination model. Groups of BALB/c mice were primed and boosted (day 28) with a combined diphtheria (D), tetanus (T), acellular pertussis (aP) vaccine (DTaP) or whole cell pertussis (P) vaccine (DTP) and the immune status was followed over time. Levels of pertussis specific IgG, induced after primary and booster immunization, peaked at day 98 to decline thereafter. This was not paralleled by a decay, but rather an increase in BM resident specific PC, over time (>1 year). In contrast, splenic B(mem) peaked after booster immunization to decline till background levels. Late recall of immunological memory more than 1 year after primary and booster vaccination, however, did reveal a rapid proliferative response of pre-existing B(mem) but failed to evoke an anamnestic IgG response. A combination of waning P-antigen specific IgG production by PC and poor functions of the B(mem) compartment such as self-maintenance and anamnestic IgG responses could be a hallmark of waning pertussis immunity. A better understanding of the mechanisms of limited immunological memory to pertussis may help to improve current vaccines.
authors.affiliation: Laboratory of Vaccine Research, Netherlands Vaccine Institute, Bilthoven, The Netherlands.
authors.forename: Rachel M
authors.initials: RM
authors.lastname: Stenger
authors.forename: Mieke
authors.initials: M
authors.lastname: Smits
authors.forename: Betsy
authors.initials: B
authors.lastname: Kuipers
authors.forename: Jacqueline
authors.initials: J
authors.lastname: van Gaans-van den Brink
authors.forename: Martien
authors.initials: M
authors.lastname: Poelen
authors.forename: Claire J P
authors.initials: CJ
authors.lastname: Boog
authors.forename: Cécile A C M
authors.initials: CA
authors.lastname: van Els
mesh_terms: D018829:Adhesins, Bacterial / Q000276:immunology; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D000915:Antibody Affinity; D000917:Antibody Formation; D001402:B-Lymphocytes / Q000276:immunology*; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology; D001886:Bordetella pertussis / Q000276:immunology*; D015721:Diphtheria-Tetanus-Pertussis Vaccine / Q000276:immunology; D022681:Diphtheria-Tetanus-acellular Pertussis Vaccines / Q000276:immunology; D005260:Female; D007074:Immunoglobulin G / Q000097:blood; D007156:Immunologic Memory; D051379:Mice; D008807:Mice, Inbred BALB C; D037342:Pertussis Toxin / Q000276:immunology; D013047:Specific Pathogen-Free Organisms; D013997:Time Factors; D010566:Virulence Factors, Bordetella / Q000276:immunology; D014917:Whooping Cough / Q000276:immunology*
chemical_list: D018829:Adhesins, Bacterial; D000907:Antibodies, Bacterial; D001425:Bacterial Outer Membrane Proteins; D015721:Diphtheria-Tetanus-Pertussis Vaccine; D022681:Diphtheria-Tetanus-acellular Pertussis Vaccines; D007074:Immunoglobulin G; D010566:Virulence Factors, Bordetella; C065273:filamentous hemagglutinin adhesin, Bordetella pertussis; C068929:pertactin; D037342:Pertussis Toxin