CTIM-07. PHASE II RANDOMIZED, BLINDED, PLACEBO-CONTROLLED TRIAL TESTING PP65 CMV MRNA DENDRITIC CELL VACCINE AND TETANUS-DIPHTHERIA TOXOID FOR NEWLY DIAGNOSED GBM (ATTAC II, NCT02465268)
Ontology highlight
ABSTRACT:
SUBMITTER:
PROVIDER: S-EPMC9660708 | biostudies-literature | 2022 Nov
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:The skin is immunologically very potent because of the high number of antigen-presenting cells in the dermis and epidermis, and is therefore considered to be very suitable for vaccination. However, the skin's physical barrier, the stratum corneum, prevents foreign substances, including vaccines, from entering the skin. Microneedles, which are needle-like structures with dimensions in the micrometer range, form a relatively new approach to circumvent the stratum corneum, allowing for minimally invasive and pain-free vaccination. In this study, we tested ceramic nanoporous microneedle arrays (npMNAs), representing a novel microneedle-based drug delivery technology, for their ability to deliver the subunit vaccines diphtheria toxoid (DT) and tetanus toxoid (TT) intradermally. First, the piercing ability of the ceramic (alumina) npMNAs, which contained over 100 microneedles per array, a length of 475 µm, and an average pore size of 80 nm, was evaluated in mouse skin. Then, the hydrodynamic diameters of DT and TT and the loading of DT, TT, and imiquimod into, and subsequent release from the npMNAs were assessed in vitro. It was shown that DT and TT were successfully loaded into the tips of the ceramic nanoporous microneedles, and by using near-infrared fluorescently labeled antigens, we found that DT and TT were released following piercing of the antigen-loaded npMNAs into ex vivo murine skin. Finally, the application of DT- and TT-loaded npMNAs onto mouse skin in vivo led to the induction of antigen-specific antibodies, with titers similar to those obtained upon subcutaneous immunization with a similar dose. In conclusion, we show for the first time, the potential of npMNAs for intradermal (ID) immunization with subunit vaccines, which opens possibilities for future ID vaccination designs.
| S-EPMC5770646 | biostudies-literature
Project description:In light of waning immunity to pertussis following receipt of tetanus toxoid, reduced diphtheria toxoid and acellular pertussis (Tdap) vaccine, maintaining protection may require repeated Tdap vaccination. We evaluated the safety of repeated doses of tetanus-containing vaccine in 68 915 nonpregnant adolescents and adults in the Vaccine Safety Datalink population who had received an initial dose of Tdap. Compared with 7521 subjects who received a subsequent dose of tetanus toxoid, reduced diphtheria (Td) vaccine, the 61 394 subjects who received a subsequent dose of Tdap did not have significantly elevated risk of medical visits for seizure, cranial nerve disorders, limb swelling, pain in limb, cellulitis, paralytic syndromes, or encephalopathy/encephalitis/meningitis. These results suggest that repeated Tdap vaccination has acceptable safety relative to Tdap vaccination followed by Td vaccination.
| S-EPMC6541919 | biostudies-literature
Project description:ObjectiveTetanus 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.Study designPregnant 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.Results374 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).ConclusionTdap 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.
| S-EPMC6675450 | biostudies-literature
Project description:An observational post-licensure (Phase IV) retrospective large-database safety study was conducted at Kaiser Permanente, a US integrated medical care organization, to assess the safety of Tetanus Toxoid, Reduced Diphtheria Toxoid and 5-Component Acellular Pertussis Vaccine (Tdap5) administered as part of routine healthcare among adolescents and adults. We evaluated incidence rates of various clinical events resulting in outpatient clinic, emergency department (ED), and hospital visits during various time intervals (windows) following Tdap5 vaccination using 2 pharmacoepidemiological methods (risk interval and historic cohort) and several screening thresholds. Plausible outcomes of interest with elevated incidence rate ratios (IRRs) were further evaluated by reviewing individual patient records to confirm the diagnosis, timing (temporal relationship), alternative etiology, and other health record details to discern possible relatedness of the health events to vaccination. Overall, 124,139 people received Tdap5 vaccine from September 2005 through mid-October 2006, and 203,154 in the comparison cohort received a tetanus and diphtheria toxoid adsorbed vaccine (and no live virus vaccine) during the year prior to initiation of this study. In the outpatient, ED and hospital databases, respectively, we identified 11/26, 179/700 and 187/700 unique health outcomes with IRRs significantly >1.0. Among the same unique health outcomes in the outpatient, ED, and hospital databases, 9, 146, and 385, respectively, had IRRs significantly <1.0. Further scrutiny of the outcomes with elevated IRRs did not reveal unexpected signals of adverse outcomes related to vaccination. In conclusion, Tdap5 vaccine was found to be safe among this large population of adolescents and adults.
| S-EPMC5137522 | biostudies-literature
Project description:IntroductionIn 2017, aligned with global World Health Organization tetanus guidelines, Vietnam prepared evidence to support a recommendation to introduce the tetanus-diphtheria (Td) vaccine into routine immunization. This study aimed to provide evidence on the costs and budgetary impact of the potential replacement of the tetanus-toxoid (TT) vaccine with the Td vaccine, considering different possible delivery strategies.MethodWe used an activity-based ingredients costing approach to estimate the 2017 program costs of providing TT vaccination to girls aged 15-16 years and conducting Td campaigns in outbreak areas. We performed a budget impact analysis for 2018-2025 using the cost per dose estimates based on the current delivery of these vaccines. We assumed complete cessation of TT vaccination of girls aged 15-16 years and a transition period where Td outbreak control campaigns would still occur. Td vaccine was assumed to be provided to children aged 7 years using either facility- or school-based delivery or combined facility- and school-based delivery.ResultsThe delivery cost per dose for current TT vaccination for girls aged 15-16 years was US$1.49 for school-based delivery, US$1.76 for facility-based delivery, and US$3.86 for delivery via outreach. Td vaccination through campaigns was estimated to cost US$3.56/dose. During 2018-2025, replacing the TT vaccine for girls aged 15-16 years with the Td vaccine for children aged 7 years is estimated to save US$4.61 million in immunization delivery costs if a school-based delivery strategy is used or US$1.04 million if facility-based delivery is used.ConclusionCompared to the current plan, delivery of Td routine vaccination via a school-based strategy was the most cost saving. These results were used in late 2019 to support the delivery of Td vaccination using a school-based delivery strategy for children aged 7 years in 30 Northern provinces in Vietnam.
| S-EPMC9053159 | biostudies-literature
Project description:The time course of whole blood gene expression was determined in healthy adult human participants who were randomised to receive either a single intramuscular immunisation with Boostrix vaccine (characteristics: treatment = BOOSTRIX) or equivalent volume saline control (characteristics: treatment = PLACEBOD2). Participants are identified who reported having had an immunisation with Boostrix within the past 5 years (characteristics: recent boostrix = 1).
2022-01-07 | GSE124842 | GEO
Project description:To examine the uptake of prenatal tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) immunization among pregnant women in the United States.Using MarketScan data, we conducted a historical cohort study among pregnant women with employer-based commercial insurance in the United States who delivered between January 1, 2010, and December 31, 2014. We examined temporal trends of uptake, predictors of uptake, and timing of Tdap immunization.Among 1,222,384 eligible pregnancies in 1,147,711 women, receipt of prenatal Tdap immunization increased from 0.0% of women who delivered in January 2010 to 9.8% who delivered in October 2012 (the date of the recommendation by the Advisory Committee on Immunization Practices for Tdap during every pregnancy) to 44.4% who delivered in December 2014. Among women who received Tdap during pregnancy, the majority were immunized between 27 weeks and 36 6/7 weeks of gestation per the Advisory Committee on Immunization Practices recommendation. In multivariable analyses among women who delivered between November 2012 and December 2014, rates of prenatal Tdap immunization were lower for women younger than 25 years of age (eg, 20-24 compared with 30-34 years rate ratio [RR] 0.83, 95% confidence interval [CI] 0.85-0.88), with other children (eg, three compared with zero children: RR 0.86, 95% CI 0.84-0.88), residing in the South compared with the Midwest (RR 0.81, 95% CI 0.80-0.82), or with emergency department visits in early pregnancy (RR 0.93, 95% CI 0.92-0.95). The proportion of pregnant women who received prenatal Tdap increased with increasing gestational age at birth.By the end of 2014, fewer than half of pregnant women in the United States were receiving prenatal Tdap immunization. Implementation and dissemination strategies are needed to increase Tdap coverage among pregnant women, especially those who are young, have other children, or reside in the South.
| S-EPMC5364044 | biostudies-literature
Project description:BackgroundIncidence of whooping cough is increasing in Korea. Since 2011, occurrence among adolescents and adults has risen putting vulnerable neonates at risk. National immunization guidelines now include Tdap (tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis) vaccination during pregnancy and as a cocooning strategy (i.e., vaccinating adults and adolescents in contact with neonates). This study assessed post-marketing Tdap (Boostrix®, GSK, Belgium) vaccine safety in subjects ≥ 10 years.MethodsThis open, non-comparative multi-center study was conducted over six years at 10 hospitals in Korea. Subjects received Tdap in normal clinical practice according to local prescribing information. All adverse events (AEs) were recorded, classified as expected or unexpected, and severity and relationship to Tdap were assessed.ResultsThe analysis included 672 Korean subjects (mean age, 44 years; range, 11-81), 451 were women and 211 were pregnant. Ninety subjects experienced 124 AEs (incidence 13.39%) of which six were serious AEs (SAEs) assessed as not related to vaccination, and 51 were non-SAEs related to vaccination (mostly administration site reactions). Overall 65/124 AEs were unexpected; the most common were 14 constipation, 5 dyspepsia, 4 common cold and 4 premature labor cases. One case of common cold was assessed as possibly related to vaccination. Pregnancy outcome was 'live infant, no apparent congenital anomaly' in 195 subjects (92.42%) or 'lost to follow-up' in 16 subjects.ConclusionTdap administration to Korean subjects ≥ 10 years, including pregnant women, for the prevention of diphtheria, tetanus and pertussis was shown to have a well-tolerated safety profile.Trial registrationClinicalTrials.gov Identifier: NCT01929291.
| S-EPMC6439203 | biostudies-literature
Project description:Opioid use disorder (OUD) is a serious health problem that has dramatically increased over the last decade. Although current therapies for the management of OUD can be effective, they have limitations. The complementary strategy to combat the opioid crisis is the development of a conjugate vaccine to generate high affinity antibodies in order to neutralize opioids in circulation before reaching the brain. The components of an opioid vaccine include an opioid hapten (6-AmHap) that is conjugated to a carrier protein (tetanus toxoid) with the addition of adjuvants (Army Liposome Formulation adsorbed to aluminum hydroxide-ALFA). There is no consensus in the literature as to whether preexisting immunity to the carrier protein may impact the immunogenicity of the conjugate vaccine by inducing an enhanced or suppressed immune response to the hapten. Here, we investigated whether pre-exposure to tetanus toxoid would affect the immunogenicity and efficacy of the heroin vaccine, TT-6-AmHap. Mice were primed with diphtheria, tetanus, and acellular pertussis (DTaP) vaccine at weeks -4 and -2, then immunized with TT-6-AmHap vaccine at weeks 0, 3, and 6. Using ELISA and behavioral assays, we found that preexisting immunity to tetanus toxoid had no influence on the immunogenicity and efficacy of the TT-6-AmHap vaccine.
| S-EPMC8229309 | biostudies-literature
Project description:BackgroundLocal reactions are the most commonly reported adverse events following tetanus and diphtheria toxoid (Td) vaccine and the risk of local reactions may increase with number of prior Td vaccinations.MethodsTo estimate the risk of medically attended local reactions following Td vaccination in adolescents and young adults we conducted a six-year retrospective cohort study assessing 436,828 Td vaccinations given to persons 9 through 25 years of age in the Vaccine Safety Datalink population from 1999 through 2004.ResultsOverall, the estimated risk of a medically attended local reaction was 3.6 events per 10,000 Td vaccinations. The lowest risk (2.8 events per 10,000 vaccinations) was found in the 11 to 15 year old age group. In comparison with that group, the event risks were significantly higher in both the 9 to 10 and 21 to 25 year old age groups. The risk of a local reaction was significantly higher in persons who had received another tetanus and diphtheria toxoid containing vaccine (TDCV) in the previous five years (incidence rate ratio, 2.9; 95% confidence interval, 1.2 to 7.2). Twenty-eight percent of persons with a local reaction to Td vaccine were prescribed antibiotics.ConclusionMedically attended local reactions were uncommon following Td vaccination. The risk of those reactions varied by age and by prior receipt of TDCVs. These findings provide a point of reference for future evaluations of the safety profile of newer vaccines containing tetanus or diphtheria toxoid.
| S-EPMC2765445 | biostudies-literature