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

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.

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Pertussis-Specific Memory B-Cell and Humoral IgG Responses in Adolescents after a Fifth Consecutive Dose of Acellular Pertussis Vaccine

Clinical and Vaccine Immunology ◽

10.1128/cvi.00280-14 ◽

2014 ◽

Vol 21 (9) ◽

pp. 1301-1308 ◽

Cited By ~ 7

Author(s):

Maja Jahnmatz ◽

Margaretha Ljungman ◽

Eva Netterlid ◽

Maria C. Jenmalm ◽

Lennart Nilsson ◽

...

Keyword(s):

B Cell ◽

Pertussis Vaccine ◽

Pertussis Toxin ◽

Acellular Pertussis Vaccine ◽

Memory B Cell ◽

Cell Responses ◽

Component Group ◽

Specific Memory ◽

Consecutive Dose ◽

Serum Igg Levels

ABSTRACTIn order to impede the increase in pertussis incidence in the adolescent group, a school-leaving booster dose administered at the age of 14 to 16 years will be introduced in Sweden in 2016. Preceding this introduction, an open-label, randomized, multicenter, clinical trial without a control group and with blinded analysis was performed, investigating both safety and immunogenicity. Reported here are the memory B-cell and serological responses detected in a smaller cohort (n= 34) of the 230 subjects recruited to the study. All subjects had received primary vaccination consisting of three doses of diphtheria–tetanus–5-component pertussis (DTaP5) vaccine, at 3, 5, and 12 months of age, and a tetanus–low-dose diphtheria–5-component pertussis (Tdap5) vaccine booster at 5.5 years. In this study, the subjects were randomly assigned and received either a Tdap1 or Tdap5 booster. Of the 230 participants, 34 subjects had samples available for evaluation of IgG-producing memory B-cell responses. Both vaccine groups had significant increases in pertussis toxin-specific serum IgG levels, but only the 1-component group showed significant increases in pertussis toxin-specific memory B cells. The 5-component group had significant increases in filamentous hemagglutinin- and pertactin-specific memory B-cell and serum IgG levels; these were not seen in the 1-component group, as expected. In conclusion, this study shows that a 5th consecutive dose of an acellular pertussis vaccine induces B-cell responses in vaccinated adolescents. (This study has been registered at EudraCT under registration no. 2008-008195-13 and at ClinicalTrials.gov under registration no. NCT00870350.)

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Primary Immunization of Infants With an Acellular Pertussis Vaccine in a Double-Blind Randomized Clinical Trial

PEDIATRICS ◽

10.1542/peds.82.3.293 ◽

1988 ◽

Vol 82 (3) ◽

pp. 293-299

Author(s):

Margareta Blennow ◽

Marta Granström ◽

Eva Jäätmaa ◽

Patrick Olin

Keyword(s):

Clinical Trial ◽

Randomized Clinical Trial ◽

Pertussis Vaccine ◽

Acellular Pertussis Vaccine ◽

Cell Vaccine ◽

Primary Immunization ◽

Double Blind ◽

Whole Cell ◽

Whole Cell Vaccine ◽

Acellular Vaccine

The rate of adverse reactions and the immunogenicity of a two-component acellular pertussis vaccine as compared with a plain whole-cell vaccine and a placebo were evaluated for primary immunization in 319 6-month-old infants in a double-blind randomized clinical trial. The acellular vaccine produced few and mild systemic and local reactions. Fever (≥38°C) occurred in 6% to 8% of acellular vaccinees as opposed to 25% to 37% of whole-cell vaccinees. Redness (≥1 cm) appeared in 2% to 13% of the acellular vaccine and 24% to 32% of the whole-cell vaccine recipients. Antibody response to pertussis toxin measured in a neutralization test was obtained in 97% to 100% of the infants receiving either two or three doses of the acellular vaccine as compared to 59% after three doses of whole-cell vaccine.

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Acellular pertussis vaccine composed of genetically inactivated pertussis toxin: Safety and immunogenicity in 12- to 24- and 2- to 4-month-old children

The Journal of Pediatrics ◽

10.1016/s0022-3476(05)80227-6 ◽

1992 ◽

Vol 120 (5) ◽

pp. 680-685 ◽

Cited By ~ 33

Author(s):

Audino Podda ◽

Erminia Carapella De Luca ◽

Lucina Titone ◽

Anna Maria Casadei ◽

Antonio Cascio ◽

...

Keyword(s):

Pertussis Vaccine ◽

Pertussis Toxin ◽

Acellular Pertussis Vaccine

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Seroprevalence of Pertussis Toxin Antibody in Manisa Province of Turkey, After Six Years Implementation of Acellular Pertussis Vaccine

Mikrobiyoloji Bulteni ◽

10.5578/mb.57534 ◽

2018 ◽

Vol 2018 (2) ◽

pp. 180-189 ◽

Cited By ~ 1

Author(s):

Özgen Alpay ÖZBEK ◽

İbrahim Mehmet Ali ÖKTEM ◽

Can Hüseyin HEKİMOĞLU ◽

Özgür SEKRETER ◽

Mestan EMEK ◽

...

Keyword(s):

Pertussis Vaccine ◽

Pertussis Toxin ◽

Acellular Pertussis Vaccine

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Acellular Pertussis Vaccine from Antigens of Freshly Isolated and Vaccine Strains of Bordetella pertussis with Different Genotypic Characteristics

Epidemiology and Vaccinal Prevention ◽

10.31631/2073-3046-2021-20-4-68-72 ◽

2021 ◽

Vol 20 (4) ◽

pp. 68-72

Author(s):

E. M. Zaitsev ◽

I. G. Bazhanova ◽

M. V. Britsina ◽

N. U. Mertsalova ◽

M. N. Ozeretskovskaya

Keyword(s):

Pertussis Vaccine ◽

Bordetella Pertussis ◽

The Body ◽

Acellular Pertussis Vaccine ◽

Protective Activity ◽

Igg Antibody ◽

Protective Antigens ◽

Promoter Gene ◽

Preclinical And Clinical Studies ◽

Genotypic Characteristics

Relevance. The development of effective and safe vaccines for pertussis prevention remains an urgent public health challenge.Aim. To study the protective activity and safety of acellular pertussis vaccine (AcPV) containing a complex of protective antigens from freshly isolated and vaccine strains of Bordetella pertussis.Materials and methods. Freshly isolated (No. 287, and No. 317) and vaccine (No. 305 and No. 475) B. pertussis strains with «non-vaccine» and «vaccine» allelic variants of the pertussis toxin (PT) subunit A gene, the PT promoter gene, the pertactin gene, the fimbria 2 gene, and the fimbria 3 gene strains were used for the production of AcPV.Results. All the studied variants of AcPV were harmless in the test of changes in the body weight of mice and sensitivity to histamine. The protective activity of AcPV3 (strains No. 287, No. 317 and No. 305) and AcPV1 (strains No. 287, No. 305 and No. 475) was higher than that of AcPV2 (strains No. 317, No. 305, and No. 475). IgG antibody titers to PT were also higher in mice immunized with AcPV1 and AcPV3.Conclusion. The higher protective activity of AcPV3 and AcPV1 may be associated with the genotype of strain No. 287, which has a ptxP3 PT promoter and is characterized by an increased level of PT production and high virulence. The most promising for further preclinical and clinical studies is AcPV3, which contains 2/3 of the antigens of the dominant «non-vaccine» genotype and 1/3 of the «vaccine» genotype, corresponding to the genes of PT, pertactin and fimbria to the currently circulating B. pertussis strains.

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