Pertussis toxin neutralizing antibody response after an acellular booster vaccination in Dutch and Finnish participants of different age groups

Knuutila, Aapo; Versteegen, Pauline; Barkoff, Alex‐Mikael; Gageldonk, Pieter G. M. van; Mertsola, Jussi; Berbers, Guy A. M.; He, Qiushui; Consortium, Periscope

doi:10.1080/22221751.2022.2053364

Cited by 7 publications

(4 citation statements)

References 42 publications

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“…Another study, with a slightly different approach, found higher vaccine responses in participants with higher baseline antibody concentrations ( 50 ). Furthermore, similar results with baseline IgG-Ptx antibody concentrations have been observed for Ptx neutralising antibody titres ( 51 ).…”

Section: Discussionsupporting

confidence: 82%

Memory B Cell Activation Induced by Pertussis Booster Vaccination in Four Age Groups of Three Countries

et al. 2022

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BackgroundImmunogenicity of acellular pertussis (aP) vaccines is conventionally assessed by measuring antibody responses but antibody concentrations wane quickly after vaccination. Memory B cells, however, are critical in sustaining long-term protection and therefore may be an important factor when assessing pertussis immunity after vaccination.AimWe studied pertussis specific memory B cell (re)activation induced by an aP booster vaccination in four different age groups within three countries.Materials and methodsFrom a phase IV longitudinal interventional study, 268 participants across Finland, the Netherlands and the United Kingdom were included and received a 3-component pertussis booster vaccine: children (7-10y, n=53), adolescents (11-15y, n=66), young adults (20-34y, n=74), and older adults (60-70y, n=75). Memory B cells at baseline, day 28, and 1 year post-vaccination were measured by a pertussis toxin (Ptx), filamentous haemagglutinin (FHA), and pertactin (Prn) specific ELISpot assay. Antibody results measured previously were available for comparison. Furthermore, study participants were distributed into groups based on their baseline memory B cell frequencies, vaccine responses were monitored between these groups.ResultsGeometric mean (GM) memory B cell frequencies for pertussis antigens at baseline were low. At 28 days post-vaccination, these frequencies increased within each age group and were still elevated one year post-booster compared to baseline. Highest frequencies at day 28 were found within adolescents (GM: 5, 21, and 13, for Ptx, FHA and Prn, respectively) and lowest within older adults (GM: 2, 9, and 3, respectively). Moderate to strong correlations between memory B cell frequencies at day 28 and antibody concentrations at day 28 and 1 year were observed for Prn. Memory B cell frequencies > 1 per 100,000 PBMCs at baseline were associated with significantly higher memory responses after 28 days and 1 year.ConclusionsAn aP booster vaccine (re)activated memory B cells in all age groups. Still elevated memory B cell frequencies after one year indicates enhanced immunological memory. However, antigen specific memory B cell activation seems weaker in older adults, which might reflect immunosenescence. Furthermore, the presence of circulating memory B cells at baseline positively affects memory B cell responses. This study was registered at www.clinicaltrialsregister.eu: No. 2016-003678-42.

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Section: Discussionsupporting

confidence: 82%

Memory B Cell Activation Induced by Pertussis Booster Vaccination in Four Age Groups of Three Countries

et al. 2022

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“…A dose of antigen representing maternal immunization was applied to the system at three representative gestational ages tvax = 10, 20, and 30 weeks to stimulate antibody secreting cell proliferation and anti-pertussis toxin IgG (α-PT IgG) secretion and transfer to the fetus (Fig 5C). Though the correlate of protection for pertussis infection still remains elusive, some possible roles of IgG in pertussis infection include neutralization and opsonophagocytosis (40,41). For the purposes of this study, we assumed that neutralizing antibodies confers protection against pertussis toxin in the neonate and therefore the optimal tvax is defined as the gestational age at immunization resulting in the highest α-PT IgG titer in the fetus at birth.…”

Section: Optimal Tdap Vaccine Schedules Depend On Gestational Age And...mentioning

confidence: 99%

“…Based on a simple kinetic reaction model, the inter-subclass competition can be described by the following closed-form equation: Optimal Gestational age (weeks) fetal α-PT IgG (μM) We next performed simulations over a range of possible immunization times to determine the optimal tvax for newborns born at different weeks of gestation (Fig 5D). Though the correlate of protection for pertussis infection still remains elusive, some possible roles of IgG in pertussis infection include neutralization and opsonophagocytosis (48,49). For the purposes of this study, we assumed that neutralizing antibodies confer protection against pertussis toxin in the neonate and therefore the optimal tvax is defined as the gestational age at immunization resulting in the highest α-PT IgG titer in the fetus at birth.…”

Section: Igg Subclasses Compete For Receptor-mediated Transcytosismentioning

confidence: 99%

Quantitative mechanistic model reveals key determinants of placental IgG transfer and informs prenatal immunization strategies

Erdogan

Dolatshahi

2023

Preprint

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Transplacental antibody transfer is crucially important in shaping neonatal immunity. Recently, prenatal maternal immunization has been employed to boost pathogen-specific immunoglobulin G (IgG) transfer to the fetus. Multiple factors have been implicated in antibody transfer, but how these key dynamic regulators work together to elicit the observed selectivity is pertinent to engineering vaccines for mothers to optimally immunize their newborns. Here, we present the first quantitative mechanistic model to uncover the determinants of placental antibody transfer and inform personalized immunization approaches. We identified placental FcγRIIb primarily expressed by endothelial cells as a limiting factor in this receptor-mediated transfer, which plays a key role in promoting preferential transport of subclasses IgG1, IgG3, and IgG4, but not IgG2. Integrated computational modeling and in vitro experiments reveal that IgG subclass abundance, Fc receptor (FcR) binding affinity, and FcR abundance in syncytiotrophoblasts and endothelial cells contribute to inter-subclass competition and potentially inter- and intra-patient antibody transfer heterogeneity. We utilize this model as an in silico immunization testbed, unveiling an opportunity for precision prenatal immunization approaches that account for a patient's anticipated gestational length, vaccine-induced IgG subclass, and placental FcR expression. By combining a computational model of maternal vaccination with this placental transfer model, we identified the optimal gestational age range for vaccination that maximizes the titer of antibody in the newborn. This optimum vaccination time varies with gestational age, placental properties, and vaccine-specific dynamics. This computational approach provides new perspectives on the dynamics of maternal-fetal antibody transfer in humans and potential avenues to optimize prenatal vaccinations that promote neonatal immunity.

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“…We next performed simulations over a range of possible immunization times to determine the optimal t vax for newborns born at different weeks of gestation (Fig 5D). Though the correlate of protection for pertussis infection still remains elusive, some possible roles of IgG in pertussis infection include neutralization and opsonophagocytosis [48,49]. For the purposes of this study, we assumed that neutralizing antibodies confer protection against pertussis toxin in the neonate and therefore the optimal t vax is defined as the gestational age at immunization resulting in the highest α-PT IgG titer in the fetus at birth.…”

Section: Optimal Tdap Vaccine Strategies Depend On Gestational Age Ki...mentioning

confidence: 99%

Quantitative mechanistic model reveals key determinants of placental IgG transfer and informs prenatal immunization strategies

Wessel,

Dolatshahi

2023

PLoS Comput Biol

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Transplacental antibody transfer is crucially important in shaping neonatal immunity. Recently, prenatal maternal immunization has been employed to boost pathogen-specific immunoglobulin G (IgG) transfer to the fetus. Multiple factors have been implicated in antibody transfer, but how these key regulators work together to elicit selective transfer is pertinent to engineering vaccines for mothers to optimally immunize their newborns. Here, we present the first quantitative mechanistic model to uncover the determinants of placental antibody transfer and inform personalized immunization approaches. We identified placental FcγRIIb expressed by endothelial cells as a limiting factor in receptor-mediated transfer, which plays a key role in promoting preferential transport of subclasses IgG1, IgG3, and IgG4, but not IgG2. Integrated computational modeling and in vitro experiments reveal that IgG subclass abundance, Fc receptor (FcR) binding affinity, and FcR abundance in syncytiotrophoblasts and endothelial cells contribute to inter-subclass competition and potentially inter- and intra-patient antibody transfer heterogeneity. We developed an in silico prenatal vaccine testbed by combining a computational model of maternal vaccination with this placental transfer model using the tetanus, diphtheria, and acellular pertussis (Tdap) vaccine as a case study. Model simulations unveiled precision prenatal immunization opportunities that account for a patient’s anticipated gestational length, placental size, and FcR expression by modulating vaccine timing, dosage, and adjuvant. This computational approach provides new perspectives on the dynamics of maternal-fetal antibody transfer in humans and potential avenues to optimize prenatal vaccinations that promote neonatal immunity.

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Pertussis toxin neutralizing antibody response after an acellular booster vaccination in Dutch and Finnish participants of different age groups

Cited by 7 publications

References 42 publications

Memory B Cell Activation Induced by Pertussis Booster Vaccination in Four Age Groups of Three Countries

Memory B Cell Activation Induced by Pertussis Booster Vaccination in Four Age Groups of Three Countries

Quantitative mechanistic model reveals key determinants of placental IgG transfer and informs prenatal immunization strategies

Quantitative mechanistic model reveals key determinants of placental IgG transfer and informs prenatal immunization strategies

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