title: Modelling anti-pertussis toxin IgG antibody decay following primary and preschool vaccination with an acellular pertussis vaccine in UK subjects using a modified oral fluid assay.
abstract: Recent vaccination with pertussis vaccine can confound serological and oral fluid (OF) assays targeting anti-pertussis toxin (anti-PT) IgG antibodies as a marker of recent infection. This study sought to establish the minimum potentially confounding time period based on experimental data to assist interpretation from such samples submitted from UK subjects for pertussis diagnosis. Anti-PT IgG antibody response and decay were measured post-vaccination using a modified OF IgG antibody-capture ELISA (GACELISA). Data were obtained from 72 infants after the third acellular pertussis vaccine dose in the primary schedule (4 months of age) and from 119 children after the single dose at preschool age (3 years 4 months to 5 years 8 months of age). Specimens were taken at approximately 1 month intervals for 9 months post-primary immunization (third dose) and 13 months post-preschool booster (PSB). The modified GACELISA demonstrated a sensitivity of 52/56 (92.9 %: 95 % CI 82.7-98.0) and a specificity of 120/128 (93.8 %: 95 % CI 88.0-97.3) and showed good agreement with the National Reference Laboratory standard anti-PT IgG serum ELISA (rank correlation = 0.80) and the original OF assay (rank correlation = 0.79). Modelling of the decline in antibody titres showed a reduction of 54 % and 34 % for each doubling of time after day 14 for the post-third primary dose and post-PSB subjects, respectively. These data suggest that the minimum confounding time period is approximately 300 days for samples obtained post-primary immunization and at least 3 years for samples submitted from UK children following immunization with the PSB. These data will greatly assist the interpretation of single high diagnostic anti-PT IgG titres by allowing an estimate of the positive predictive value, when the number of days post-immunization and prevalence are known or assumed.
authors.affiliation: Public Health England-Respiratory and Vaccine Preventable Bacteria Reference Unit, Colindale, London, UK.
authors.forename: Norman K
authors.initials: NK
authors.lastname: Fry
authors.affiliation: Public Health England-Respiratory and Vaccine Preventable Bacteria Reference Unit, Colindale, London, UK.
authors.forename: David J
authors.initials: DJ
authors.lastname: Litt
authors.affiliation: Public Health England-Respiratory and Vaccine Preventable Bacteria Reference Unit, Colindale, London, UK.
authors.forename: John
authors.initials: J
authors.lastname: Duncan
authors.affiliation: Public Health England-Respiratory and Vaccine Preventable Bacteria Reference Unit, Colindale, London, UK.
authors.forename: Lalita
authors.initials: L
authors.lastname: Vaghji
authors.affiliation: Public Health England-Virus Reference Department, Colindale, London, UK.
authors.forename: Lenesha
authors.initials: L
authors.lastname: Warrener
authors.affiliation: Public Health England-Virus Reference Department, Colindale, London, UK.
authors.forename: Dhanraj
authors.initials: D
authors.lastname: Samuel
authors.affiliation: Public Health England-Statistics, Modelling and Economics Department, Health Protection Services, Colindale, London, UK.
authors.forename: Nick
authors.initials: N
authors.lastname: Andrews
authors.affiliation: University of Oxford, Department of Primary Care Health Sciences, Oxford, UK.
authors.forename: Anthony
authors.initials: A
authors.lastname: Harnden
authors.affiliation: Public Health England-Respiratory and Vaccine Preventable Bacteria Reference Unit, Colindale, London, UK.
authors.forename: Timothy G
authors.initials: TG
authors.lastname: Harrison
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood* / Q000276:immunology; D058846:Antibodies, Monoclonal, Murine-Derived; D000917:Antibody Formation; D001886:Bordetella pertussis / Q000276:immunology; D002675:Child, Preschool; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007115:Immunization Schedule; D007117:Immunization, Secondary; D007074:Immunoglobulin G / Q000097:blood* / Q000276:immunology; D007223:Infant; D051379:Mice; D008807:Mice, Inbred BALB C; D037342:Pertussis Toxin / Q000276:immunology*; D010567:Pertussis Vaccine / Q000008:administration & dosage* / Q000276:immunology; D011237:Predictive Value of Tests; D012680:Sensitivity and Specificity; D013997:Time Factors; D006113:United Kingdom; D022282:Vaccines, Acellular / Q000008:administration & dosage* / Q000276:immunology; D014917:Whooping Cough / Q000517:prevention & control
chemical_list: D000907:Antibodies, Bacterial; D058846:Antibodies, Monoclonal, Murine-Derived; D007074:Immunoglobulin G; D010567:Pertussis Vaccine; D022282:Vaccines, Acellular; D037342:Pertussis Toxin