Mass Spectrometry-Based Quantification of the Antigens in Aluminum Hydroxide-Adjuvanted Diphtheria-Tetanus-Acellular-Pertussis Combination Vaccines
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SUBMITTER: van der Maas L
PROVIDER: S-EPMC9323524 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ImportanceThe United States has experienced a nationwide resurgence of pertussis since the mid-1970s, despite high estimated vaccine coverage. Short-lived immunity induced by diphtheria-tetanus-acellular pertussis (DTaP) vaccines in young children is widely believed to be responsible for this growing burden, but the duration of protection conferred by DTaP vaccines remains incompletely quantified.ObjectiveTo assess the duration of immunity and the effectiveness of DTaP vaccines in US children.Design, setting, and participantsA mathematical, age-structured model of pertussis transmission, previously validated empirically on incidence data in Massachusetts, was used in this simulation study to assess the duration of DTaP immunity most consistent with the empirical values of the relative increase in the odds of acquiring pertussis from recent epidemiologic studies in the United States. The study included 5 simulated cohorts of children born between January 1, 2001, and December 31, 2005, followed up between the ages of 5 and 9 years (study period, January 1, 2006, to December 31, 2014). Statistical analysis was performed from May 1 to December 1, 2017.InterventionsVaccination with DTaP according to the US immunization schedule, with a range of assumptions regarding the degree of waning immunity.Main outcomes and measuresVaccine effectiveness and relative change in the odds of acquiring pertussis (odds ratio) in children aged 5 to 9 years, duration of DTaP immunity, and vaccine population-level impact.ResultsThis study found a marked association between the degree of waning immunity, vaccine effectiveness, and the odds ratio. Counterintuitively, the odds ratio was positively associated with vaccine effectiveness, as a consequence of nonlinear, age-assortative transmission dynamics. Based on the empirical odds ratios (1.33; 95% CI, 1.23-1.43), it was estimated that vaccine effectiveness exceeded 75% in children aged 5 to 9 years and that more than 65% of children remained immune to pertussis 5 years after the last DTaP dose.Conclusions and relevanceThe results of this study suggest that temporal trends in the odds of acquiring pertussis are an unreliable measure of the durability of vaccine-induced protection. They further demonstrate that DTaP vaccines confer imperfect, but long-lived protection. Control strategies should be based on the best available estimates of vaccine properties and the age structure of the transmission network.
| S-EPMC6547082 | biostudies-literature
Project description: Not available
| S-EPMC4288310 | biostudies-literature
Project description:BackgroundAdministering inactivated influenza vaccine (IIV), 13-valent pneumococcal conjugate vaccine (PCV13), and diphtheria-tetanus-acellular pertussis (DTaP) vaccine together has been associated with increased risk for febrile seizure after vaccination. We assessed the effect of administering IIV at a separate visit from PCV13 and DTaP on postvaccination fever.MethodsIn 2017-2018, children aged 12 to 16 months were randomly assigned to receive study vaccines simultaneously or sequentially. They had 2 study visits 2 weeks apart; nonstudy vaccines were permitted at visit 1. The simultaneous group received PCV13, DTaP, and quadrivalent IIV (IIV4) at visit 1 and no vaccines at visit 2. The sequential group received PCV13 and DTaP at visit 1 and IIV4 at visit 2. Participants were monitored for fever (?38°C) and antipyretic use during the 8 days after visits.ResultsThere were 110 children randomly assigned to the simultaneous group and 111 children to the sequential group; 90% received ?1 nonstudy vaccine at visit 1. Similar proportions of children experienced fever on days 1 to 2 after visits 1 and 2 combined (simultaneous [8.1%] versus sequential [9.3%]; adjusted relative risk = 0.87 [95% confidence interval 0.36-2.10]). During days 1 to 2 after visit 1, more children in the simultaneous group received antipyretics (37.4% vs 22.4%; P = .020).ConclusionsIn our study, delaying IIV4 administration by 2 weeks in children receiving DTaP and PCV13 did not reduce fever occurrence after vaccination. Reevaluating this strategy to prevent fever using an IIV4 with a different composition in a future influenza season may be considered.
| S-EPMC7055925 | biostudies-literature
Project description:Despite high vaccination coverage worldwide, pertussis has re-emerged in many countries. This randomized, controlled, observer-blind phase I study and extension study in Belgium (March 2012-June 2015) assessed safety and immunogenicity of investigational acellular pertussis vaccines containing genetically detoxified pertussis toxin (PT) (NCT01529645; NCT02382913). 420 healthy adults (average age: 26.8 ± 5.5 years, 60% female) were randomized to 1 of 10 vaccine groups: 3 investigational aP vaccines (containing pertussis antigens PT, filamentous hemagglutinin [FHA] and pertactin [PRN] at different dosages), 6 investigational TdaP (additionally containing tetanus toxoid [TT] and diphtheria toxoid [DT]), and 1 TdaP comparator containing chemically inactivated PT. Antibody responses were evaluated on days 1, 8, 30, 180, 365, and approximately 3 years post-booster vaccination. Cell-mediated immune responses and PT neutralization were evaluated in a subset of participants in pre-selected groups. Local and systemic adverse events (AEs), and unsolicited AEs were collected through day 7 and 30, respectively; serious AEs and AEs leading to study withdrawal were collected through day 365 post-vaccination. Antibody responses against pertussis antigens peaked at day 30 post-vaccination and then declined but remained above baseline level at approximately 3 years post-vaccination. Responses to FHA and PRN were correlated to antigen dose. Antibody responses specific to PT, toxin neutralization activity and persistence induced by investigational formulations were similar or significantly higher than the licensed vaccine, despite lower PT doses. Of 15 serious AEs, none were considered vaccination-related; 1 led to study withdrawal (premature labor, day 364; aP4 group). This study confirmed the potential benefits of genetically detoxified PT antigen. All investigational study formulations were well tolerated.
| S-EPMC5791588 | biostudies-literature
Project description:The Advisory Committee on Immunization Practices recommends administering diphtheria, tetanus and acellular pertussis (DTaP) vaccines to children at 2, 4, 6, 15-18 months, and 4-6 y of age; preferably with the same-brand vaccine for the whole series. We estimated age-appropriate DTaP dose completion and the proportion of children receiving a "mixed" DTaP vaccination series (ie, including DTaP vaccines from ? 2 brands) across the 3 milestones. Commercially-insured children born between 01/01/2003 and 04/30/2011 were identified from United States health insurance claims data and assigned to ? 1 of 3 study cohorts based on the duration of continuous health plan enrollment: 1) birth to <8 months; 2) birth to <20 months; 3) birth to <7 years. Dose completion and brand mixing of the first 3, first 4 or all 5 doses were measured in the respective cohorts. Administered DTaP vaccinations were identified in claims data and classified by brand (based on vaccine components and manufacturer). The analysis included children who received ? 2 DTaP vaccinations and had known brand information for all doses. Age-appropriate dose completion was 77% with 3 doses (<8 months cohort), 71% with 4 doses (<20 months cohort), and 85% with 5 doses (<7 years cohort). Mixed DTaP series were received by 4.7% (95% confidence interval [CI]: 4.6%-4.7%) in the <8 months cohort, 29.0% (95% CI: 28.6%-29.4%) in the <20 months cohort, and 39.0% (95% CI: 34.5, 43.6) in the <7 years cohort. DTaP mixing was just 4.7% for the first 3 doses but subsequently increased with the number of administered doses.
| S-EPMC4514255 | biostudies-literature
Project description:To assess pregnancy and birth outcomes in infants born to women who did or did not receive tetanus, diphtheria, acellular pertussis (Tdap) vaccine during pregnancy.Retrospective cohort. Pregnant women 12-45 years of age who received Tdap at Intermountain Healthcare facilities and their infants were identified and compared with mother-infant pairs without documented Tdap from May 2005 through August 2009. Primary measures included pregnancy outcomes and infant health outcomes at birth through 12 months.From 162,448 pregnancies we identified 138 women (0.08%) with documented Tdap administration during pregnancy (cases); 552 pregnant women without documented Tdap were randomly selected as controls. Of 138 immunized women, 63% received Tdap in the first trimester and 37% after. Tdap was given most commonly as wound prophylaxis. The incidence of spontaneous or elective abortion was no greater in Tdap cases than in controls. There were no significant differences in preterm delivery, gestational age, or birth weight between groups. One or more congenital anomaly was identified in 3.7% (95% CI 1.2%-8.5%) of case infants and 4.4% (95% CI 2.7%-6.5%) of control infants (P = .749). In infants born to women receiving Tdap during pregnancy, 3.6% (0.8%-10.2%) had International Classification of Diseases, Ninth Revision, Clinical Modification diagnoses consistent with complex chronic conditions within 12 months compared with 10.4% (95% CI 7.2%-14.4%) of infants of controls (P = .054).Documented Tdap administration during pregnancy was uncommon and occurred most often in the first trimester as prophylaxis following trauma. No increase in adverse outcomes was identified in infants born to women receiving Tdap compared with infants of controls.
| S-EPMC4102585 | biostudies-other
Project description:INTRODUCTION:It is recommended that all pregnant women in the U.S. receive tetanus, diphtheria, acellular pertussis (Tdap) immunization to prevent infant pertussis. This study's objective was to examine the clinical effectiveness of prenatal Tdap, and whether effectiveness varies by gestational age at immunization. METHODS:A nationwide cohort study of pregnant women with deliveries in 2010-2014 and their infants was performed. Commercial insurance claims data were analyzed in 2016-2017 to identify Tdap receipt by the pregnant women, and hospitalizations and outpatient visits for pertussis in their infants until the infants reached 18 months of age. Pertussis occurrence was compared between infants of mothers who received prenatal Tdap (overall and stratified by gestational age at administration) and infants of unvaccinated mothers. RESULTS:There were 675,167 mother-infant pairs in the cohort. Among infants whose mothers received prenatal Tdap, the rate of pertussis was 43% lower (hazard ratio=0.57, 95% CI=0.35, 0.92) than infants whose mothers did not receive prenatal or postpartum Tdap; this reduction was consistent across pertussis definitions (hazard ratio for inpatient-only pertussis=0.32, 95% CI=0.11, 0.91). Pertussis rates were also lower for infants whose mothers received Tdap during the third trimester. Infants whose mothers received Tdap at <27 weeks of gestation did not experience reductions in pertussis rates (hazard ratio for pertussis=1.10, 95% CI=0.54, 2.25). CONCLUSIONS:Infants of mothers who received prenatal Tdap experienced half the rate of pertussis as compared with infants of unimmunized mothers. These results do not provide evidence to support changing the currently recommended timing of Tdap administration in pregnancy.
| S-EPMC6054882 | biostudies-literature
Project description:Background: Optimal timing of gestational tetanus-diphtheria-acellular pertussis (Tdap) vaccination is not well-defined. No well-established specific anti-pertussis antibody level correlates with protection, suggesting the importance of antibody quality such as avidity. We aimed to determine the effect of timing of vaccination with Tdap in pregnancy on the avidity of cord anti-pertussis toxin (PT) immunoglobulin G (IgG). Methods: Prospective study of newborns in a tertiary hospital (Melbourne, Australia) born to women vaccinated with Tdap in pregnancy. Ammonium thiocyanate was used as a bond-breaking agent to measure the avidity of anti-PT IgG using concentrations between 0.25 M (to measure low avidity antibodies) and 3 M (to measure very high avidity antibodies). Anti-PT IgG levels achieved at each ammonium thiocyanate concentration in cord samples of women vaccinated during 28-32 weeks gestation (WG) vs. 33-36 WG, and women vaccinated 5-12 vs. 1-4 weeks prior to delivery were compared using t-tests. Results: Newborns of women vaccinated with Tdap during 28-32 WG (n = 43) had statistically significant higher concentrations of medium and high avidity anti-PT IgG compared with newborns of women vaccinated during 33-36 WG (n = 47), 11.6 IU/ml (95% CI, 8.8-15.2) IU/ml vs. 6.7 IU/ml (95% CI, 5.2-8.6) and 10.1 IU/ml (95% CI, 7.4-13.8) vs. 5.7 (95% CI, 3.6-8.9) IU/ml (p = 0.007 and p = 0.035), respectively. Newborns of women vaccinated 5-12 weeks before delivery (n = 64) had statistically significant higher concentrations of high and very high avidity anti-PT IgG compared with newborns of women vaccinated within 4 weeks before delivery (n = 25), 10.3 IU/mL (95% CI, 7.9-13.4) vs. 3.3 IU/mL (95% CI, 1.7-6.4), 12.6 IU/mL (95% CI, 9.4-16.9) vs. 4.3 IU/mL (95% CI, 2.2-8.5) (all p < 0.03), respectively. Conclusions: Quantification of levels of anti-PT IgG with different avidities demonstrated that pertussis vaccination 5-12 weeks before delivery was associated with higher anti-PT IgG avidity compared with vaccination within 4 weeks before delivery. Pertussis vaccination during 28-32 WG was associated with higher anti-PT IgG avidity compared with vaccination during 33-36 WG, supporting vaccination at 28-32 over 33-36 WG for optimal protection against pertussis in infancy.
| S-EPMC6798090 | biostudies-literature
Project description:BackgroundThe necessity of the tetanus-reduced dose diphtheria-acellular pertussis (Tdap) vaccine in adolescence and adults has been emphasized since the resurgence of small-scale pertussis in Korea and worldwide due to the waning effect of the vaccine and variant pathogenic stains in the late 1990s. GreenCross Pharma (GC Pharma), a Korean company, developed the Tdap vaccine GC3111 in 2010. Recently, they enhanced the vaccine, GC3111, produced previously in 2010 to reinforce the antibody response against filamentous hemagglutinin (FHA). In this study, immunogenicity and efficacy of the enhanced Tdap vaccine compared and evaluated with two Tdap vaccines, GC3111 vaccine produced in 2010 previously and commercially available Tdap vaccine in a murine model.MethodsTwo tests groups and positive control group of Balb/c mice were primed with two doses of the diphtheria-tetanus-acellular pertussis (DTaP) vaccine followed by a single booster Tdap vaccine at 9 week using the commercially available Tdap vaccine or 2 Tdap vaccines from GC Pharma (GC3111, enhanced GC3111). Humoral response was assessed 1 week before and 2 and 4 weeks after Tdap booster vaccination. The enhanced GC3111 generated similar humoral response compare to the commercial vaccine for filamentous hemagglutinin (FHA). The interferon gamma (IFN-γ) (Th1), interleukin 5 (IL-5) (Th2) and interleukin 17 (IL-17) (Th17) cytokines were assessed 4 weeks after booster vaccination by stimulation with three simulators: heat inactivated Bordetella pertussis (hBp), vaccine antigens, and hBp mixed with antigens (hBp + antigen). A bacterial challenge test was performed 4 weeks after booster vaccination.ResultsRegarding cell-mediated immunity, cytokine secretion differed among the three simulators. However, no difference was found between two test groups and positive control group. All the vaccinated groups indicated a Th1 or Th1/Th2 response. On Day 5 post-bacterial challenge, B. pertussis colonies were absent in the lungs in two test groups and positive control group.ConclusionsOur results confirmed the immunogenicity of GC Pharma's Tdap vaccine; enhanced GC3111 was equivalent to the presently used commercial vaccine in terms of humoral response as well as cell-mediated cytokine expression.
| S-EPMC8506493 | biostudies-literature
Project description:BackgroundTo reduce the risk of pertussis-related morbidity and mortality in early life, an increasing number of countries recommend maternal pertussis vaccination. However, there is limited knowledge about half-lives of vaccine-induced pertussis-specific maternal antibodies, especially in preterm infants, and factors potentially influencing them.MethodsWe compared 2 different approaches to provide estimates of the half-lives of pertussis-specific maternal antibodies in infants and explored potential effects on the half-life in 2 studies. In the first approach, we estimated the half-lives per child and used these estimates as responses in linear models. In the second approach, we used linear mixed effect models on a log2 transformed scale of the longitudinal data to use the inverse of the time parameter as an estimate for the half-lives.ResultsBoth approaches provided similar results. The identified covariates partly explain differences in half-life estimates. The strongest evidence we observed was a difference between term and preterm infants, with the preterm infants showing a longer half-life. Among others, a longer interval between vaccination and delivery increases the half-life.ConclusionsSeveral variables influence the decay speed of maternal antibodies. Both approaches have advantages and disadvantages, while the choice is secondary when assessing the half-life of pertussis-specific antibodies.Clinical trials registrationNCT02408926 and NCT02511327.
| S-EPMC10681861 | biostudies-literature