Evaluation of Anti-PT Antibody Response after Pertussis Vaccination and Infection: The Importance of Both Quantity and Quality

Barkoff, Alex‐Mikael; Knuutila, Aapo; Mertsola, Jussi; He, Qiushui

doi:10.3390/toxins13080508

Cited by 12 publications

(12 citation statements)

References 123 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Repeated antigenic stimulation leads to the selection of B cells that bear a receptor able to bind the antigen with a higher avidity, as a result of clonal selection in germinal centers. Previous studies showed how antibody avidity for pertussis toxin increases over time after infection or vaccination, then declining over time [ 19 ]. Analyzing the immune response to a measles-vectored chikungunya vaccine, Tschismarov et al [ 20 ] reported an increase in avidity with the second dose.…”

Section: Discussionmentioning

confidence: 99%

Repeated SARS-CoV-2 vaccination in cancer patients treated with immune checkpoint inhibitors: induction of high-avidity anti-RBD neutralizing antibodies

et al. 2023

View full text Add to dashboard Cite

Background Cancer patients are more vulnerable to COVID-19 and are thus given high priority in vaccination campaigns. In solid cancer patients treated with checkpoint inhibitors, we evaluated the amount of anti-RBD and neutralizing antibodies and antibody avidity after two or three doses of the vaccine. Methods Thirty-eight solid cancer patients, 15 untreated hematological patients and 21 healthy subjects were enrolled in the study. Blood was collected before the first dose (T0), 21 days after the second (T2) and in 18 solid cancer patients also 15 days after the third dose of vaccine (T3). IgG, IgM and IgA anti-RBD antibodies were detected by ELISA. Neutralizing antibodies were measured testing the inhibition of RBD binding to ACE2. Antibody avidity was evaluated in 18 patients by a urea avidity ELISA. Results IgG anti-RBD antibodies were produced in 65.8% of the cancer patients at T2, and in 60% of hematological patients at levels lower than healthy controls. IgM and IgA anti-RBD antibodies were also produced in 5.3% and 21% cancer patients, respectively. At T3, a significant increase in anti-RBD IgG levels was observed. Neutralizing antibodies were produced in 68.4% of cancer patients as compared with 93% of untreated hematological patients and 100% of controls, at titers lower than in healthy subjects. At T3, neutralizing antibodies and avidity of IgG anti-RBD increased; 6/18 patients negative at T2 developed neutralizing antibodies at T3. Conclusion The data indicate that in cancer patients mRNA vaccine induces high avidity anti-RBD antibodies and neutralizing antibodies that increase after the third dose. The process of induction and selection of high-affinity antibodies is apparently unaffected by the treatment with anti-PD-1 or anti-PD-L1 antibodies.

show abstract

Section: Discussionmentioning

confidence: 99%

Repeated SARS-CoV-2 vaccination in cancer patients treated with immune checkpoint inhibitors: induction of high-avidity anti-RBD neutralizing antibodies

et al. 2023

View full text Add to dashboard Cite

show abstract

“…There are two other potential sources of variance between assays. Samples with a marginally weaker antibody avidity [28] may have a lower signal response, as the sample has a very limited time to react with the PT antigen on the test line during the flow of the sample in comparison to ELISA [24]. Second, the porous nitrocellulose material that the sample passes through in the LF test strip and the microtitre wells used in the ELISA are physically very different materials, which may lead to interference in antigen binding [29].…”

Section: Resultsmentioning

confidence: 99%

Oral fluid-based lateral flow point-of-care assays for pertussis serology

Knuutila

Duncan²,

Li³

et al. 2023

Journal of Medical Microbiology

Self Cite

View full text Add to dashboard Cite

Introduction. Current serological diagnosis of pertussis is usually performed by ELISA, which is typically performed in larger diagnostic or reference laboratories, requires trained staff, and due to sample batching may have longer turnaround times. Hypothesis and Aim. A rapid point-of-care (POC) assay for pertussis serology would aid in both the diagnosis and surveillance of the disease. Methodology. A quantitative lateral flow (LF)-based immunoassay with fluorescent Eu-nanoparticle reporters was developed for the detection of anti-pertussis toxin (PT) and adenylate cyclase toxin (ACT) antibodies from oral fluid samples (N=100), from suspected pertussis cases with respiratory symptoms. Results. LF assay results were compared to those obtained with anti-PT IgG oral fluid ELISA. For an ELISA cut-off value of 50 arbitrary units, the overall agreement between the assays was 91/100 (91 %), the sensitivity was 63/70 (90 %) and the specificity was 28/30 (93 %). No ACT-specific antibodies were detected from oral fluid samples; however, the signal readout positively correlated to those patients with high anti-PT IgG antibodies. Conclusion. The developed LF assay was a specific, sensitive and rapid test for serological diagnosis of pertussis with anti-PT antibodies and is a suitable POC test using oral fluid samples.

show abstract

“…The CHO cell assay for pertussis toxin and Vero cell assay for diphtheria toxin is laborious, semi-quantitative, and less sensitive than ELISA-based readouts. Various studies have reported a positive correlation between the concentration of IgG antibodies and neutralization antibody titers ( 30 , 36 – 38 ). We also studied the agreement between the IgG concentrations estimated by bead-based assay and toxin-neutralization antibodies for pertussis and diphtheria toxin antigens.…”

Section: Discussionmentioning

confidence: 99%

“…The highest dilution of sera, which showed cluster neutralization, was recorded as the sample titer. A positive score was assigned when 10 or more CHO cell clusters were evident within a single well ( 30 ).…”

Section: Methodsmentioning

confidence: 99%

Multiplexed bead-based assay for the simultaneous quantification of human serum IgG antibodies to tetanus, diphtheria, pertussis toxin, filamentous hemagglutinin, and pertactin

et al. 2023

View full text Add to dashboard Cite

BackgroundLuminex bead-based assays offer multiplexing to test antibodies against multiple antigens simultaneously; however, this requires validation using internationally certified reference standards. Therefore, there is an urgent need to characterize existing reference standards for the standardization of multiplex immunoassays (MIAs). Here, we report the development and validation of an MIA for the simultaneous estimation of levels of human serum immunoglobulin G (IgG) antibodies for pertussis toxin (PT), filamentous hemagglutinin (FHA), pertactin (PRN), diphtheria toxoid (DT), and tetanus toxoid (TT).MethodsThe MIA was assessed using a panel of human serum samples and WHO reference standards. The WHO reference standards were also studied for suitability in the MIA. Purified antigens (PT, FHA, PRN, DT, and TT) were coupled to the spectrally unique magnetic carboxylated microspheres. The method was validated in accordance with the United States Food and Drug Administration (US FDA), European Medicines Agency (EMA), and the International Committee of Harmonization Multidisciplinary (ICH M10) guidelines, and parameters such as precision, accuracy, dilutional linearity, assay range, robustness, and stability were assessed. Method agreements with commercially available IgG enzyme-linked immunosorbent assay (ELISA) assays were also evaluated. In addition, the study assessed the level of correlation between the IgG levels estimated by the MIA and the cell-based neutralizing antibody assays for PT and DT.ResultsWe identified that an equimix of WHO international standards (i.e., 06/142, 10/262, and TE-3) afforded the best dynamic range for all the antigens in the MIA. For all five antigens, we observed that the back-fitted recoveries using the four-parameter logistic (4-PL) regression fits ranged between 80% and 120% for all calibration levels, and the percentage coefficient of variation (% CV) was < 20%. In addition, the difference in mean fluorescence intensity (MFI) between the monoplex and multiplex format was < 10% for each antigen, indicating no crosstalk among the beads. The MIA also showed good agreement with conventional and commercially available assays, and a positive correlation (> 0.75) with toxin neutralization assays for PT and DT was observed.ConclusionThe MIA that was calibrated in accordance with WHO reference standards demonstrated increased sensitivity, reproducibility, and high throughput capabilities, allowing for the design of robust studies that evaluate both natural and vaccine-induced immunity.

show abstract

Evaluation of Anti-PT Antibody Response after Pertussis Vaccination and Infection: The Importance of Both Quantity and Quality

Cited by 12 publications

References 123 publications

Repeated SARS-CoV-2 vaccination in cancer patients treated with immune checkpoint inhibitors: induction of high-avidity anti-RBD neutralizing antibodies

Repeated SARS-CoV-2 vaccination in cancer patients treated with immune checkpoint inhibitors: induction of high-avidity anti-RBD neutralizing antibodies

Oral fluid-based lateral flow point-of-care assays for pertussis serology

Multiplexed bead-based assay for the simultaneous quantification of human serum IgG antibodies to tetanus, diphtheria, pertussis toxin, filamentous hemagglutinin, and pertactin

Contact Info

Product

Resources

About