•To avoid a global pertussis resurgence, booster Tdap immunization is recommended.•Global shortages of acellular pertussis vaccines have been reported.•Safety and immunogenicity of SIIPL Tdap was ...compared to an approved Tdap vaccine.•SIIPL Tdap immune responses were non-inferior to comparator Tdap vaccine.•SIIPL Tdap was safe and well tolerated.
This study assessed the safety and immunogenicity of a new booster vaccine against tetanus, diphtheria, and pertussis manufactured by Serum Institute of India Pvt. Ltd (SIIPL Tdap).
The Phase II/III trial was randomized (2:1), observer blinded and active controlled. Healthy subjects aged 4–65 years received a single dose of either SIIPL Tdap or comparator Tdap vaccine (Boostrix®, GlaxoSmithKline, Belgium), and were followed-up for 30 days. Blood samples for safety and immunogenicity assessments were collected pre-vaccination and on day 30 post-vaccination. The study assessed safety and reactogenicity of SIIPL Tdap compared to the comparator Tdap as well as the co-primary immunogenicity outcomes: (i) seroprotection rates against diphtheria toxoid (DT) and tetanus toxoid (TT) and (ii) the booster response rates against pertussis toxoid (PT), filamentous hemagglutinin (FHA) and pertactin (PRN) 30 days post-vaccination in all study subjects. A margin of −10 % was used for non-inferiority testing. Secondary outcomes included the booster response rates against DT and TT, seropositivity rates against pertussis antigens, and antibody geometric mean concentrations (GMCs) for all vaccine components.
At Day 30 post-vaccination, SIIPL Tdap was assessed as non-inferior to the comparator Tdap in terms of: i) seroprotection rates against DT (94.4 % vs. 94.9 %) and TT (99.9 % vs. 100 %) and ii) pertussis booster response rates (93.8 % vs. 88.4 % anti-PT, 89.7 % vs. 90.9 % anti-FHA and 86.3 % vs. 84.4 % anti-PRN), for SIIPL Tdap versus comparator Tdap, respectively. GMCs for anti-PT and anti-PRN were higher in subjects vaccinated with SIIPL Tdap compared to comparator Tdap. All other secondary outcomes were comparable. The overall frequency of local and systemic solicited AEs was comparable; no treatment related SAEs were reported.
Booster vaccination with SIIPL Tdap was non-inferior to comparator Tdap with respect to the immunogenicity of the vaccine components and was equally well tolerated.
EudraCT number: 2019-002706-46.
Abstract This article presents the World Health Organization’s (WHO) recommendations on the use of tetanus toxoid (TT) vaccines excerpted from the WHO position paper on tetanus vaccines – February ...2017, published in the Weekly Epidemiological Record 1 . This position paper replaces the May 2006 WHO position paper on tetanus vaccines (Tetanus vaccines: WHO position paper, 2006). The position paper summarizes the recent developments in the field of tetanus prevention and provides revised guidance on the optimal timing of recommended tetanus vaccine booster doses. Footnotes to this paper provide a number of core references including references to grading tables that assess the quality of the scientific evidence, and to the evidence-to-recommendation table. In accordance with its mandate to provide guidance to Member States on health policy matters, WHO issues a series of regularly updated position papers on vaccines and combinations of vaccines against diseases that have an international public health impact. These papers are concerned primarily with the use of vaccines in large-scale immunization programmes; they summarize essential background information on diseases and vaccines, and conclude with WHO's current position on the use of vaccines in the global context. Recommendations on the use of TT-containing vaccines (TTCVs) were discussed by SAGE in October 2016; evidence presented at the meeting can be accessed at: http://www.who.int/immunization/sage/meetings/2016/october/presentations_background_docs/en/.
Background. We estimated the vaccine effectiveness (VE) of tetanus-diphtheria-acellular pertussis vaccine (Tdap) for preventing pertussis among adolescents during a statewide outbreak of pertussis in ...Wisconsin during 2012. Methods. We used the population-based Wisconsin Immunization Registry (WIR) to construct a cohort of Wisconsin residents born during 1998-2000 and collect Tdap vaccination histories. Reports of laboratory-confirmed pertussis with onset during 2012 were matched to WIR clients. Incidence rate ratios (IRRs) of pertussis and Tdap VE estimates (1 - IRR)*100%, by year of Tdap vaccine receipt and brand (Boostrix/Adacel), were estimated using Poisson regression. Results. Tdap VE decreased with increasing time since receipt, with VEs of 75.3% (95% confidence interval CI, 55.2%-86.5%) for receipt during 2012,68.2% (95% CI, 60.9%-74.1%) for receipt during 2011, 34.5% (95% CI, 19.9%-46.4%) for receipt during 2010, and 11.9% (95% CI, -11.1% to 30.1%) for receipt during 2009/2008; point estimates were higher among Boostrix recipients than among Adacel recipients. Among Tdap recipients, increasing time since receipt was associated with increased risk, and receipt of Boostrix (vs Adacel) was associated with decreased risk of pertussis (adjusted IRR, 0.62 95% CI, .52-74). Conclusions. Our results demonstrate waning immunity following vaccination with either Tdap brand. Boostrix was more effective than Adacel in preventing pertussis in our cohort, but these findings may not be generalizable to adolescent cohorts that received different diphtheria-tetanus-acellular pertussis vaccines (DTaP) during childhood and should be further examined in studies that include childhood DTaP history.
Maternal and neonatal tetanus Thwaites, C Louise, Dr; Beeching, Nicholas J, Dr; Newton, Charles R, Prof
The Lancet (British edition),
01/2015, Letnik:
385, Številka:
9965
Journal Article
Recenzirano
Odprti dostop
Summary Maternal and neonatal tetanus is still a substantial but preventable cause of mortality in many developing countries. Case fatality from these diseases remains high and treatment is limited ...by scarcity of resources and effective drug treatments. The Maternal and Neonatal Tetanus Elimination Initiative, launched by WHO and its partners, has made substantial progress in eliminating maternal and neonatal tetanus. Sustained emphasis on improvement of vaccination coverage, birth hygiene, and surveillance, with specific approaches in high-risk areas, has meant that the incidence of the disease continues to fall. Despite this progress, an estimated 58 000 neonates and an unknown number of mothers die every year from tetanus. As of June, 2014, 24 countries are still to eliminate the disease. Maintenance of elimination needs ongoing vaccination programmes and improved public health infrastructure.
Routine use of whole-cell pertussis (wP) vaccines was suspended in some countries in the 1970s and 1980s because of concerns about adverse effects. Following this action, there was a resurgence of ...whooping cough. Acellular pertussis (aP) vaccines, containing purified or recombinant Bordetella pertussis (B. pertussis) antigens, were developed in the hope that they would be as effective, but less reactogenic than the whole-cell vaccines. This is an update of a Cochrane review first published in 1999, and previously updated in 2012. In this update, we included no new studies.
To assess the efficacy and safety of acellular pertussis vaccines in children and to compare them with the whole-cell vaccines.
We searched CENTRAL (2013, Issue 12), MEDLINE (1950 to January week 2, 2014), EMBASE (1974 to January 2014), Biosis Previews (2009 to January 2014) and CINAHL (2009 to January 2014).
We selected double-blind randomised efficacy and safety trials of aP vaccines in children up to six years old, with active follow-up of participants and laboratory verification of pertussis cases.
Two review authors independently extracted data and assessed the risk of bias in the studies. Differences in trial design precluded a meta-analysis of the efficacy data. We pooled the safety data from individual trials using a random-effects meta-analysis model.
We included six efficacy trials with a total of 46,283 participants and 52 safety trials with a total of 136,541 participants. Most of the safety trials did not report the methods for random sequence generation, allocation concealment and blinding, which made it difficult to assess the risk of bias in the studies. The efficacy of multi-component (≥ three) vaccines varied from 84% to 85% in preventing typical whooping cough (characterised by 21 or more consecutive days of paroxysmal cough with confirmation of B. pertussis infection by culture, appropriate serology or contact with a household member who has culture-confirmed pertussis), and from 71% to 78% in preventing mild pertussis disease (characterised by seven or more consecutive days of cough with confirmation of B. pertussis infection by culture or appropriate serology). In contrast, the efficacy of one- and two-component vaccines varied from 59% to 78% against typical whooping cough and from 41% to 58% against mild pertussis disease. Multi-component acellular vaccines are more effective than low-efficacy whole-cell vaccines, but may be less effective than the highest-efficacy whole-cell vaccines. Most systemic and local adverse events were significantly less common with aP vaccines than with wP vaccines for the primary series as well as for the booster dose.
Multi-component (≥ three) aP vaccines are effective in preventing whooping cough in children. Multi-component aP vaccines have higher efficacy than low-efficacy wP vaccines, but they may be less efficacious than the highest-efficacy wP vaccines. Acellular vaccines have fewer adverse effects than whole-cell vaccines for the primary series as well as for booster doses.
•Production of a genetically detoxified, full-length tetanus toxin protein (8MTT) in Gor/MetTM E.•Coli, a strain which expresses of soluble, disulfide-bonded proteins.•8MTT was purified to > 99 % ...purity, yielding 0.5 g of 8MTT/liter of fermentation broth, with low.•Endotoxin contamination, and antigenic purity of 3500 Lf/mg of 8MTT protein nitrogen.•8MTT is an antigenicvaccine and an effective carrier protein for peptide and polysaccharide conjugates.•These studies validate 8MTT as a tetanus vaccine with modern manufacturing, regulatory, standardization, and safety requirements.
Tetanus toxoid (TTxd), developed over 100 years ago, is a clinically effective, legacy vaccine against tetanus. Due to the extreme potency of native tetanus toxin, manufacturing and regulatory efforts often focus on TTxd production, standardization, and safety, rather than product modernization. Recently, a genetically detoxified, full-length tetanus toxin protein (8MTT) was reported as a tetanus vaccine alternative to TTxd (Przedpelski et al. mBio, 2020). Here we describe the production of 8MTT in Gor/MetTM E. coli, a strain engineered to have an oxidative cytoplasm, allowing for the expression of soluble, disulfide-bonded proteins. The strain was also designed to efficiently cleave N-terminal methionine, the obligatory start amino acid for E. coli expressed proteins. 8MTT was purified as a soluble protein from the cytoplasm in a two-column protocol to > 99 % purity, yielding 0.5 g of purified 8MTT/liter of fermentation broth with low endotoxin contamination, and antigenic purity of 3500 Lf/mg protein nitrogen. Mouse immunizations showed 8MTT to be an immunogenic vaccine and effective as a carrier protein for peptide and polysaccharide conjugates. These studies validate 8MTT as commercially viable and, unlike the heterogenous tetanus toxoid, a uniform carrier protein for conjugate vaccines. The development of a recombinant, genetically detoxified toxin produced in E. coli aligns the tetanus vaccine with modern manufacturing, regulatory, standardization, and safety requirements.
Tetanus toxoid, reduced diphtheria toxoid, and acellular pertusiss (Tdap) vaccine is recommended during each pregnancy, regardless of prior receipt. Data on reactogenicity and immunogenicity, ...particularly after repeated Tdap, are limited. We compared local injection-site and systemic reactions and serologic response following Tdap in (1) pregnant and nonpregnant women and (2) pregnant women by self-reported prior Tdap receipt.
Pregnant women (gestational age 20–34 weeks) and nonpregnant women receiving Tdap were enrolled in this observational study. Injection-site and systemic reactions were assessed for one week post-vaccination. Pertussis toxin, filamentous hemagglutinin, pertactin, fimbriae, tetanus and diphtheria specific IgG antibody titers were determined by standardized enzyme-linked immunosorbent assay at baseline and 28 days post-vaccination. Reactogenicity and serologic responses were compared by pregnancy status, and within pregnant women by self-reported prior Tdap receipt.
374 pregnant and 225 nonpregnant women were vaccinated. Severe local or systemic reactions or “any” fever were uncommon (≤3% for both groups). Moderate/severe injection-site pain was significantly higher in pregnant (17.9%) versus nonpregnant (11.1%) women, but did not prompt a healthcare visit. Proportions of other moderate/severe or any severe reactions were not significantly higher in pregnant compared to nonpregnant women. Moderate/severe (including pain) and severe reactions were not significantly higher in pregnant women receiving repeat versus first-time Tdap. Antibody titers increased from baseline to post-vaccination for all vaccine antigens in pregnant and nonpregnant women; post-vaccination titers against pertussis toxin and filamentous hemagglutinin were significantly higher in nonpregnant versus pregnant women (p < 0.01).
Tdap was well-tolerated in pregnant and nonpregnant women. Pregnant women were more likely to report moderate/severe pain at the Tdap injection-site compared with nonpregnant women, but did not necessitate medical visits. Prior Tdap receipt did not increase occurrence of moderate/severe local or systemic reactions in pregnant women. Serologic responses to all vaccine antigens were robust.
Clinical Trial Registration@ClinicalTrials.gov. NCT02209623.
https://clinicaltrials.gov/ct2/show/NCT02209623.
•Five fully human neutralizing antibodies against tetanus neurotoxin were isolated from a vaccinated individual.•The neutralizing antibodies bind to different epitopes of tetanus toxoid with high ...affinities.•Three neutralizing antibodies conferred full protection in mice against tetanus neurotoxin challenge.
Clostridium tetani causes life-threatening disease by producing tetanus neurotoxin (TeNT), one of the most toxic protein substances. Toxicosis can be prevented and cured by administration of anti-TeNT neutralizing antibodies. Here, we identified a series of monoclonal antibodies (mAbs) derived from memory B cells of a healthy adult immunized with the C-terminal domain of TeNT (TeNT-Hc). Thirteen mAbs bound to both tetanus toxoid (TT) and TeNT-Hc, while two mAbs recognized only TT. VH3-23 was the most frequently used germline gene in these TT-binding mAbs, and the pairwise identity values of the VH gene sequences ranged from 27% to 69%. Three of these mAbs—T3, T7, and T9-6—completely protected mice from challenge with 2× LD50 of TeNT, and two (T2 and T18) significantly prolonged the survival time. The five neutralizing mAbs recognized distinct epitopes on TT, with binding affinities ranging from 0.123 to 11.9 nM. Our study provides promising therapeutic candidates for tetanus.
Maternal immunization with tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine could prevent infant pertussis.
To evaluate the safety and immunogenicity of Tdap ...immunization during pregnancy and its effect on infant responses to diphtheria and tetanus toxoids and acellular pertussis (DTaP) vaccine.
Phase 1-2, randomized, double-blind, placebo-controlled, clinical trial conducted from 2008 to 2012. Forty-eight pregnant women aged 18 to 45 years received Tdap (n = 33) or placebo (n = 15) at 30 to 32 weeks' gestation, with crossover immunization postpartum.
Tdap vaccination at 30 to 32 weeks' gestation or postpartum.
Primary outcomes were maternal and infant adverse events, pertussis illness, and infant growth and development until age 13 months. Secondary outcomes were antibody concentrations in pregnant women before and 4 weeks after Tdap immunization or placebo, at delivery and 2 months' postpartum, and in infants at birth, at 2 months, and after the third and fourth doses of DTaP.
No Tdap-associated serious adverse events occurred in women or infants. Injection site reactions after Tdap immunization were reported in 26 (78.8% 95% CI, 61.1%-91.0%) and 12 (80% 95% CI, 51.9%-95.7%) pregnant and postpartum women, respectively (P > .99). Systemic symptoms were reported in 12 (36.4% 95% CI, 20.4%-54.9%) and 11 (73.3% 95% CI, 44.9%-92.2%) pregnant and postpartum women, respectively (P = .03). Growth and development were similar in both infant groups. No cases of pertussis occurred. Significantly higher concentrations of pertussis antibodies were measured at delivery in women who received Tdap during pregnancy vs postpartum (eg, pertussis toxin antibodies: 51.0 EU/mL 95% CI, 37.1-70.1 and 9.1 EU/mL 95% CI, 4.6-17.8, respectively; P < .001) and in their infants at birth (68.8 EU/mL 95% CI, 52.1-90.8 and 14.0 EU/mL 95% CI, 7.3-26.9, respectively; P < .001) and at age 2 months (20.6 EU/mL 95% CI, 14.4-29.6 and 5.3 EU/mL 95% CI, 3.0-9.4, respectively; P < .001). Antibody responses in infants born to women receiving Tdap during pregnancy were not different following the fourth dose of DTaP.
This preliminary assessment did not find an increased risk of adverse events among women who received Tdap vaccine during pregnancy or their infants. For secondary outcomes, maternal immunization with Tdap resulted in high concentrations of pertussis antibodies in infants during the first 2 months of life and did not substantially alter infant responses to DTaP. Further research is needed to provide definitive evidence of the safety and efficacy of Tdap immunization during pregnancy.
clinicaltrials.gov Identifier: NCT00707148.
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