Antibody responses to pertussis toxin display different kinetics after clinical Bordetella pertussis infection than after vaccination with an acellular pertussis vaccine

The measurement of IgG anti-pertussis toxin (IgG anti-PT) antibodies by ELISA is a frequently used method for studying the antibody responses after pertussis vaccination and after Bordetella pertussis infection. Such responses vary according to the different vaccines used as well as to the immunization and infection history of the participants. In the present study, the decay kinetics of the IgG anti-PT antibody response was determined for 71 Danish children and adults with bacteriologically confirmed B. pertussis infection and for 20 Danish adults booster-vaccinated with an acellular pertussis vaccine. For both groups, biphasic decay was seen, but the individual antibody responses varied greatly. No differences related to age were seen. Within each group, individual decay profiles showed parallel log-linear decay for the late part of the response. Antibody half-life was calculated for the late, slower part of the biphasic response curves for both groups (>5 months after diagnosis for individuals with confirmed infection; >3 months for vaccinated individuals). The median half-life for post-infection antibodies was 221 days [interquartile range (IQR) 159–314 days, 36 individuals], and the median half-life for post-vaccination antibodies was 508 days (IQR 428–616 days, 14 individuals). This difference was statistically significant (P<0.0001). Thus, in this setting, we found that the IgG anti-PT antibody decay after an infection with B. pertussis is more than twice as fast as the decay after booster vaccination with an acellular pertussis vaccine. Such knowledge of the IgG anti-PT decay kinetics is crucial for interpretation of serological data that will be used either for diagnosis or for epidemiological studies and surveillance of B. pertussis infections.

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Antibody Responses to Bordetella pertussis Fim2 or Fim3 following Immunization with a Whole-Cell, Two-Component, or Five-Component Acellular Pertussis Vaccine and following Pertussis Disease in Children in Sweden in 1997 and 2007

Clinical and Vaccine Immunology ◽

10.1128/cvi.00641-13 ◽

2013 ◽

Vol 21 (2) ◽

pp. 165-173 ◽

Cited By ~ 9

Author(s):

Hans Hallander ◽

Abdolreza Advani ◽

Frances Alexander ◽

Lennart Gustafsson ◽

Margaretha Ljungman ◽

...

Keyword(s):

Pertussis Vaccine ◽

Bordetella Pertussis ◽

Geometric Mean ◽

Acellular Pertussis Vaccine ◽

Antibody Responses ◽

Cell Vaccine ◽

Whole Cell ◽

Content Type ◽

Two Component ◽

Whole Cell Vaccine

ABSTRACTBordetella pertussisfimbriae (Fim2 and Fim3) are components of a five-component acellular pertussis vaccine (diphtheria–tetanus–acellular pertussis vaccine [DTaP5]), and antibody responses to fimbriae have been associated with protection. We analyzed the IgG responses to individual Fim2 and Fim3 in sera remaining from a Swedish placebo-controlled efficacy trial that compared a whole-cell vaccine (diphtheria-tetanus-whole-cell pertussis vaccine [DTwP]), a two-component acellular pertussis vaccine (DTaP2), and DTaP5. One month following three doses of the Fim-containing vaccines (DTwP or DTaP5), anti-Fim2 geometric mean IgG concentrations were higher than those for anti-Fim3, with a greater anti-Fim2/anti-Fim3 IgG ratio elicited by DTaP5. We also determined the responses in vaccinated children following an episode of pertussis. Those who received DTaP5 showed a large rise in anti-Fim2 IgG, reflecting the predominant Fim2 serotype at the time. In contrast, those who received DTwP showed an equal rise in anti-Fim2 and anti-Fim3 IgG concentrations, indicating that DTwP may provide a more efficient priming effect for a Fim3 response following contact withB. pertussis. Anti-Fim2 and anti-Fim3 IgG concentrations were also determined in samples from two seroprevalence studies conducted in Sweden in 1997, when no pertussis vaccine was used and Fim2 isolates predominated, and in 2007, when either DTaP2 or DTaP3 without fimbriae was used and Fim3 isolates predominated. Very similar distributions of anti-Fim2 and anti-Fim3 IgG concentrations were obtained in 1997 and 2007, except that anti-Fim3 concentrations in 1997 were lower. This observation, together with the numbers of individuals with both anti-Fim2 and anti-Fim3 IgG concentrations, strongly suggests thatB. pertussisexpresses both Fim2 and Fim3 during infection.

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Cell‐Mediated Immunity and Antibody Responses toBordetella pertussisAntigens in Children with a History of Pertussis Infection and in Recipients of an Acellular Pertussis Vaccine

The Journal of Infectious Diseases ◽

10.1086/315509 ◽

2000 ◽

Vol 181 (6) ◽

pp. 1989-1995 ◽

Cited By ~ 52

Author(s):

Clara M. Ausiello ◽

Roberto Lande ◽

Francesca Urbani ◽

Beatrice Di Carlo ◽

Paola Stefanelli ◽

...

Keyword(s):

Pertussis Vaccine ◽

Acellular Pertussis Vaccine ◽

Antibody Responses ◽

Cell Mediated Immunity ◽

Pertussis Infection ◽

History Of

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Differences in Antibody Response to Whole-Cell Pertussis Vaccines

PEDIATRICS ◽

10.1542/peds.88.5.1019 ◽

1991 ◽

Vol 88 (5) ◽

pp. 1019-1023

Author(s):

Kathryn M. Edwards ◽

Michael D. Decker ◽

Neal A. Halsey ◽

Beryl A. Koblin ◽

Timothy Townsend ◽

...

Keyword(s):

United States ◽

Pertussis Vaccine ◽

Pertussis Toxin ◽

Fold Increase ◽

The United States ◽

Acellular Pertussis Vaccine ◽

Antibody Responses ◽

Data Sets ◽

Whole Cell ◽

To Receive

It has been assumed that whole-cell pertussis vaccines (WCVs) commercially distributed in the United States are of comparable immunogenicity, as all must comply with established standards for licensure. However, we have recently noted significant differences in antibody responses between groups of infants receiving the two WCVs commercially available in the United States. In separate studies performed concurrently under similar protocols at Vanderbilt and Johns Hopkins universities, infants were randomized to receive either an acellular pertussis vaccine or WCV. The acellular pertussis vaccine used at the two sites was identical, but the WCVs were from different manufacturers. Antibody responses to acellular pertussis vaccine did not differ between the two studies; responses to WCV differed dramatically, with infants receiving the Lederle WCV producing a 46-fold increase in antibody to pertussis toxin, compared with a 2.4-fold increase for infants receiving the Connaught WCV (P = .00003). Evaluation of other comparative data sets that were available provided further support for the conclusion that the two commercially available WCVs consistently differed in their ability to induce antibody to pertussis toxin. These findings have important implications for the design and interpretation of clinical trials comparing acellular and WCV products.

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Antibody Responses to Individual Bordetella pertussis Fimbrial Antigen Fim2 or Fim3 following Immunization with the Five-Component Acellular Pertussis Vaccine or to Pertussis Disease

Clinical and Vaccine Immunology ◽

10.1128/cvi.00355-12 ◽

2012 ◽

Vol 19 (11) ◽

pp. 1776-1783 ◽

Cited By ~ 10

Author(s):

Frances Alexander ◽

Mary Matheson ◽

Norman K. Fry ◽

Briony Labram ◽

Andrew R. Gorringe

Keyword(s):

Pertussis Vaccine ◽

Bordetella Pertussis ◽

Age Groups ◽

Sampling Period ◽

Acellular Pertussis Vaccine ◽

Antibody Responses ◽

Enzyme Linked Immunosorbent Assay ◽

Content Type ◽

The United Kingdom ◽

The Individual

ABSTRACTBordetella pertussisexpresses two serologically distinct fimbriae (Fim2 and Fim3) which are included in the Sanofi Pasteur 5-component acellular pertussis vaccine, and antibody responses to these antigens have been shown to be associated with protection. Studies to date have assessed the IgG response to this vaccine using a copurified mixture of Fim2 and Fim3, and the response to the individual antigens has not been characterized. We have purified separate Fim2 and Fim3 from strains that express either Fim2 or Fim3 and have used these antigens in an enzyme-linked immunosorbent assay (ELISA) to quantify IgG responses following immunization with 5-component acellular pertussis vaccine in 15-month-old, 4- to 6-year-old, and 11- to 18-year-old subjects. All individuals showed increases in Fim2 and Fim3 IgG concentrations following immunization, with 3-fold-greater Fim2 than Fim3 IgG concentrations seen in the younger two age groups. Fim2 IgG concentrations were 1.5-fold greater than Fim3 IgG concentrations in the 11- to 18-year-olds. We have also compared Fim2 and Fim3 IgG concentrations in individuals with prolonged cough who were diagnosed as having recent pertussis using a pertussis toxin (Ptx) IgG ELISA with individuals with prolonged cough but without elevated Ptx IgG concentrations. Individuals with evidence of recent pertussis had greater Fim3 IgG concentrations, consistent with the predominant serotype of isolates obtained in the United Kingdom. However, a surprising number of individuals had moderate Fim2 IgG concentrations despite very few isolates of that serotype obtained in the sampling period.

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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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Corrigendum to ‘Antibody persistence and safety and immunogenicity of a second booster dose nine years after a first booster vaccination with a reduced antigen diphtheria-tetanus-acellular pertussis vaccine (Tdap) in adults’. [Vaccine 36 (2018) 6325–6333]

Vaccine ◽

10.1016/j.vaccine.2020.01.082 ◽

2020 ◽

Vol 38 (12) ◽

pp. 2746-2747

Author(s):

Donald Brandon ◽

Murray Kimmel ◽

Sherine O. Kuriyakose ◽

Lusiné Kostanyan ◽

Narcisa Mesaros

Keyword(s):

Pertussis Vaccine ◽

Booster Dose ◽

Booster Vaccination ◽

Acellular Pertussis Vaccine ◽

Antibody Persistence

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Human Serum Antibody Responses to Bordetella pertussis Infection and Pertussis Vaccination

The Journal of Infectious Diseases ◽

10.1093/infdis/159.2.211 ◽

1989 ◽

Vol 159 (2) ◽

pp. 211-218 ◽

Cited By ~ 48

Author(s):

M. G. Thomas ◽

K. Redhead ◽

H. P. Lambert

Keyword(s):

Human Serum ◽

Bordetella Pertussis ◽

Serum Antibody ◽

Antibody Responses ◽

Pertussis Infection

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Bordetella Pertussis Antibody Levels in DPT/Pentavalent Immunized Preschool Nigerian Children: A Cross-Sectional Study

Journal of Pediatric Infectious Diseases ◽

10.1055/s-0039-1693484 ◽

2019 ◽

Vol 15 (01) ◽

pp. 011-015

Author(s):

Glory Ekpo Bassey ◽

Emmanuel Eyo Ekanem ◽

Henry Chima Okpara ◽

Komomo Ibor Eyong

Keyword(s):

Pertussis Toxin ◽

Bordetella Pertussis ◽

Age Groups ◽

Booster Vaccination ◽

Rapid Decline ◽

Age Group ◽

Igg Antibodies ◽

Cross Sectional ◽

Nigerian Children ◽

Antibody Levels

AbstractPertussis is a vaccine-preventable disease and antibodies formed are known to decline with time. The aim of this study was to measure Bordetella pertussis/toxin immunoglobulin G (IgG) antibodies in different age groups of Nigerian children and determine the age at which booster dose may be required. A total of 422 children, aged 6 to 60 months, were tested for the presence of B. pertussis/toxin IgG antibodies by ELISA (enzyme-linked immune sorbent assay). The highest positivity rate was in the 6 to 11 months of age group, while the highest negativity rate was in the age group of 24 to 35 months. We conclude that B. Pertussis/toxin IgG antibodies response is weak in Nigerian children after three doses of DPT (diphtheria, pertussis, and tetanus)/pentavalent vaccination, and there is a rapid decline of antibody levels between 12 and 35 months. We recommend that booster vaccination should be given at 12 to 15 months of age.

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Development and Analytical Validation of an Immunoassay for Quantifying Serum Anti-Pertussis Toxin Antibodies Resulting from Bordetella pertussis Infection

Clinical and Vaccine Immunology ◽

10.1128/cvi.00248-09 ◽

2009 ◽

Vol 16 (12) ◽

pp. 1781-1788 ◽

Cited By ~ 26

Author(s):

Sandra L. Menzies ◽

Vijay Kadwad ◽

Lucia C. Pawloski ◽

Tsai-Lien Lin ◽

Andrew L. Baughman ◽

...

Keyword(s):

Pertussis Toxin ◽

Bordetella Pertussis ◽

Collaborative Study ◽

World Health ◽

Enzyme Linked Immunosorbent Assay ◽

Analytical Validation ◽

Igg Antibody ◽

Pertussis Infection ◽

Validation Parameters ◽

Health Organization

ABSTRACT Adequately sensitive and specific methods to diagnose pertussis in adolescents and adults are not widely available. Currently, no Food and Drug Administration-approved diagnostic assays are available for the serodiagnosis of Bordetella pertussis. Since concentrations of B. pertussis-specific antibodies tend to be high during the later phases of disease, a simple, rapid, easily transferable serodiagnostic test was developed. This article describes test development, initial evaluation of a prototype kit enzyme-linked immunosorbent assay (ELISA) in an interlaboratory collaborative study, and analytical validation. The data presented here demonstrate that the kit met all prespecified criteria for precision, linearity, and accuracy for samples with anti-pertussis toxin (PT) immunoglobulin G (IgG) antibody concentrations in the range of 50 to 150 ELISA units (EU)/ml, the range believed to be most relevant for serodiagnosis. The assay met the precision and linearity criteria for a wider range, namely, from 50 to 200 EU/ml; however, the accuracy criterion was not met at 200 EU/ml. When the newly adopted World Health Organization International Standard for pertussis antiserum (human) reference reagent was used to evaluate accuracy, the accuracy criteria were met from 50 to 200 international units/ml. In conclusion, the IgG anti-PT ELISA met all assay validation parameters within the range considered most relevant for serodiagnosis. This ELISA was developed and analytically validated as a user-friendly kit that can be used in both qualitative and quantitative formats. The technology for producing the kit is transferable to public health laboratories.

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