Pertussis stability

Vaccination is widely considered to be one of the most important prevention measures as a health strategy. This paper examines trends in basic childhood vaccination coverage and which country and time-dependent determinants may have influenced childhood immunization rates (1-dose BCG, 1- and 3-dose DTP (diphtheria, tetanus, pertussis), 1-dose measles, and 3-dose polio) between 1980 and 2020 across 94 countries. We identify economic, inequality, demographic, health, education, labor market, environmental, and political stability factors of immunization...

β2-Adrenoceptors (β2-ARs) are the most abundant subtype of adrenergic receptors in skeletal muscles. Their activation via a stabilization of postsynaptic architecture has beneficial effects in certain models of neuromuscular disorders. However, the ability of β2-ARs to regulate neuromuscular transmission at the presynaptic level is poorly understood. Using electrophysiological recordings and fluorescent FM dyes, we found that β2-AR activation with fenoterol enhanced an involvement of synaptic vesicles in exocytosis and neurotransmitter release during intense activity at the neuromuscular junctions of mouse diaphragm...

Since the 2000s, sporadic outbreaks of whooping cough have been reported in advanced countries, where the acellular pertussis vaccination rate is relatively high, and in developing countries. Small-scale whooping cough has also continued in many countries, due in part to the waning of immune protection after childhood vaccination, necessitating the development of an improved pertussis vaccine and vaccination program. Currently, two different production platforms are being actively pursued in Korea; one is based on the aP (acellular pertussis) vaccine purified from B...

BACKGROUND: Respiratory syncytial virus (RSV) fusion protein stabilized in the prefusion conformation (RSVPreF3) was under investigation as a maternal vaccine. METHODS: This phase 2, randomized, placebo-controlled, single-dose, multicenter study enrolled healthy, non-pregnant women, randomized 1:1:1:1:1 to five parallel groups studying RSVPreF3 (60 or 120 µg) co-administered with diphtheria, tetanus, and acellular pertussis vaccine (dTpa) or placebo, and dTpa co-administered with placebo...

As global demands for rare-earth elements (REEs) continue to grow, the biological recovery of REEs has been explored as a promising strategy, driven by potential economic and environmental benefits. It is known that calcium-binding domains, including helix-loop-helix EF hands and repeats-in-toxin (RTX) domains, can bind lanthanide ions due to their similar ionic radii and coordination preference to calcium. Recently, the lanmodulin protein from Methylorubrum extorquens was reported, which has evolved a high affinity for lanthanide ions over calcium...

We report here the development and validation of CE-SDS method for purity analysis of Acellular Pertussis vaccine components viz. purified Pertussis toxin (PTx), purified Filamentous haemagglutinin (FHA), and Pertactinantigen (PRN). The method was found to be specific and showed excellent linearity at a concentration range of 15.62 µg/mL-1000 µg/mL for purified PTx, 31.25 µg/mL-1000 µg/mL for purified FHA, and 3.9 µg/mL-1000 µg/mL for PRN antigen. Method reported limit of quantification (LOQ) 31...

BACKGROUND: Luminex 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)...

Tetanus is a bacterial infection caused by the toxin of  Clostridium tetani . While it primarily affects newborns, people with incomplete vaccination schedules, it can also impact people of any age, especially in developing countries. Even though in the last 20 years several initiatives have been implemented worldwide to reduce the impact of this disease, regions like South Asia and sub-Saharan Africa have registered mortality rates highest since 2015-2019. In Latin America, regional immunization coverage rates were reported at 89% in 2017 for diphtheria-tetanus toxoid and pertussis (DTP-3), although Costa Rica has reported decreased coverage rates of the national immunization schedule from 2019 to 2021...

Peptidoglycan (PG) is a central component of the bacterial cell wall, and the disruption of its biosynthetic pathway has been a successful antibacterial strategy for decades. PG biosynthesis is initiated in the cytoplasm through sequential reactions catalyzed by Mur enzymes that have been suggested to associate into a multimembered complex. This idea is supported by the observation that in many eubacteria, mur genes are present in a single operon within the well conserved dcw cluster, and in some cases, pairs of mur genes are fused to encode a single, chimeric polypeptide...

To improve pertussis toxin (PT) yield in B. pertussis strains for vaccine production a genetically-engineered strain (gdPT 191-134 strain) with a second copy of the genetically detoxified PT (gdPT) locus was developed. The consistency of the production and genetic stability of the strain when used for vaccine production must be established. We developed two simplex ddPCR assays with PCR systems for ptxA, the target gene present in two copies, and pgm, the reference gene present as a single copy. The ddPCR assay had sufficient precision to discriminate the copy number of the PT locus accurately in two B...

INTRODUCTION: An increased risk of chorioamnionitis in people receiving tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine during pregnancy has been reported. The importance of this association is unclear as additional study has not demonstrated increased adverse infant outcomes associated with Tdap vaccination in pregnancy. METHODS: We conducted a retrospective observational cohort study of pregnant people ages 15-49 years with singleton pregnancies ending in live birth who were members of 8 Vaccine Safety Datalink (VSD) sites during October 2016-September 2018...

Autotransporters are a large family of virulence factors found in Gram-negative bacteria that play important roles in their pathogenesis. The passenger domain of autotransporters is almost always composed of a large β-helix, with only a small portion of it being relevant to its virulence function. This has led to the hypothesis that the folding of the β-helical structure aids the secretion of the passenger domain across the Gram-negative outer membrane (OM). In this study, we used molecular dynamics simulations and enhanced sampling methods to investigate the stability and folding of the passenger domain of pertactin, an autotransporter from Bordetella pertussis...

INTRODUCTION: Global warming is slowly but surely becoming one of the greatest problems of the modern world. Heatwaves with extremely high temperatures and humidity changes are particularly dangerous as they can lead to increased mortality rates and increased side effects of certain medications. The goal of this study was to give a short review of the most critical issues healthcare professionals should be mindful of when it comes to prescription of medicines during high temperature periods...

Immunization has been considered a successful global health program that saves many persons' lives each year. The vaccines reduce the risk of getting the disease by building immunity in the body. Therefore, the constant availability of essential vaccines is an important factor in community health. One of the most important vaccines is the diphtheria vaccine, which is usually used as Multivalent diphtheria-tetanus-pertussis (DTP) combination vaccines. The production of this vaccine takes about 45 days, from the initial bacterial culture to the end of toxin production...

Introduction: The essential components of a vaccine delivery system are well-documented, but robust evidence on how and why the related processes and implementation strategies drive catalytic improvements in vaccination coverage are not well established. To address this gap, we identified critical success factors that may have led to substantial improvements in routine childhood immunization coverage in Nepal from 2000 through 2019. Methods: We identified Nepal as an exemplar in the delivery of early childhood immunization through analysis of DTP1 and DTP3 coverage data...

Biased agonism is a frontier field in G-protein coupled receptor (GPCR) research. Acquired hypocalciuric hypercalcemia (AHH) is a rare disease caused by calcium-sensing receptor (CaSR) autoantibodies, to date, showing either simple blocking or biased properties (i.e., stimulatory or blocking effects on different downstream signaling pathways). This emphasizes the importance of the Gi/o (pertussis toxin-sensitive G proteins, whose βγ subunits activate multiple signals including ERK1/2) in regulating PTH secretion...

Cerebral hypoperfusion and vascular dysfunction are closely related to common risk factors for ischemic stroke such as hypertension, dyslipidemia, diabetes, and smoking. The role of inhibitory G protein-dependent receptor (Gi PCR) signaling in regulating cerebrovascular functions remains largely elusive. We examined the importance of Gi PCR signaling in cerebral blood flow (CBF) and its stability after sudden interruption using various in vivo high-resolution magnetic resonance imaging techniques. To this end, we induced a functional knockout of Gi PCR signaling in the brain vasculature by injection of pertussis toxin (PTX)...

Adenylate Cyclase Toxin (ACT or CyaA) is one of the important virulence factors secreted by Bordetella pertussis , the bacterium causative of whooping cough. ACT debilitates host defenses by production of unregulated levels of cAMP into the cell cytosol upon delivery of its N-terminal domain with adenylate cyclase activity (AC domain) and by forming pores in the plasma membrane of macrophages. Binding of soluble toxin monomers to the plasma membrane of target cells and conversion into membrane-integrated proteins are the first and last step for these toxin activities; however, the molecular determinants in the protein or the target membrane that govern this conversion to an active toxin form are fully unknown...

BACKGROUND: Prevention of respiratory syncytial virus (RSV) disease in infants is an unmet vaccine need, and maternal immunization is a potential strategy to address this need. This study evaluated concomitant administration of RSV stabilized prefusion F subunit vaccine (RSVpreF) and tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine adsorbed (Tdap) in healthy, nonpregnant women 18‒49 years of age. METHODS: In this phase 2b, multicenter, placebo-controlled, observer-blind, noninferiority study, participants were randomized to receive RSVpreF in a range of doses and formulations with Tdap or alone, or Tdap alone...

Live vaccines are attractive vehicles for antigen delivery as a strategy to immunize against heterologous pathogens. The live vaccine MTBVAC is based on rational attenuation of Mycobacterium tuberculosis with the objective of improving BCG protection against pulmonary tuberculosis. However, the development of recombinant mycobacteria as antigen-presenting microorganisms has been hindered due to their fastidious genetic manipulation. In this study, we used MTBVAC as a genetic platform to deliver diphtheria, tetanus, or pertussis toxoids, which are the immunogenic constituents of the DTP vaccine...