Long-Term Efficacy of a Hepatitis E Vaccine Zhang, Jun; Zhang, Xue-Feng; Huang, Shou-Jie ...
New England journal of medicine/The New England journal of medicine,
03/2015, Letnik:
372, Številka:
10
Journal Article
Recenzirano
Odprti dostop
Hepatitis E virus is a common cause of illness worldwide and is associated with severe complications, especially in pregnant women. In this report, the long-term efficacy, immunogenicity, and safety ...of a hepatitis E vaccine are described.
Hepatitis E virus (HEV) is a common cause of acute hepatitis worldwide.
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HEV infection occurs in two distinct epidemiologic patterns.
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The most common pattern is waterborne infection, which is caused by HEV genotype 1 or 2 and occurs mainly in resource-limited countries, often in large, protracted outbreaks or in sporadic cases associated with high mortality among pregnant women.
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The other pattern is transmission from animals and humans, which is caused by HEV genotype 3 or 4 and occurs widely in both resource-limited and developed countries.
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Rein et al.
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estimated the incidence of hepatitis E in areas . . .
Biofilm structure and functionality depend on extracellular polymeric substances (EPS), but analytical methods for EPS often lack specificity which limits progress of biofilm research.
EPS were ...extracted from aerobic granular sludge and analyzed with frequently applied colorimetric methods. The colorimetric methods were evaluated based on their applicability for EPS analysis. EPS fractions of interest were proteins, sugars, uronic acids and phenolic compounds. The applied methods (Lowry method, bicinchoninic acid assay, phenol sulfuric acid method, carbazole sulfuric acid method) were investigated in terms of their sensitivity towards the selected standard compound. Interference of compounds present in EPS with the colorimetric methods was further evaluated. All methods showed to be highly depending on the choice of standard compound and susceptible towards interference by compounds present in EPS.
This study shows that currently used colorimetric methods are not capable of accurately characterizing EPS. More advanced methods are needed to be able to draw conclusions about biofilm composition, structure and functionality.
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•Colorimetric EPS analysis is very sensitive towards the standard selection.•Analysis of single EPS compounds is prone to interference by other EPS compounds.•EPS quantification with colorimetric methods can easily give inaccurate results.•New approaches and methods are needed to accurately characterize EPS.
Abstract
Background
The high cost and insufficient supply of human papillomavirus (HPV) vaccines have slowed the pace of controlling cervical cancer. A phase III clinical trial was conducted to ...evaluate the efficacy, safety, and immunogenicity of a novel Escherichia coli-produced bivalent HPV-16/18 vaccine.
Methods
A multicenter, randomized, double-blind trial started on November 22, 2012 in China. In total, 7372 eligible women aged 18–45 years were age-stratified and randomly assigned to receive three doses of the test or control (hepatitis E) vaccine at months 0, 1, and 6. Co-primary endpoints included high-grade genital lesions and persistent infection (over 6 months) associated with HPV-16/18. The primary analysis was performed on a per-protocol susceptible population of individuals who were negative for relevant HPV type-specific neutralizing antibodies (at day 0) and DNA (at day 0 through month 7) and who received three doses of the vaccine. This report presents data from a prespecified interim analysis used for regulatory submission.
Results
In the per-protocol cohort, the efficacies against high-grade genital lesions and persistent infection were 100.0% (95% confidence interval = 55.6% to 100.0%, 0 of 3306 in the vaccine group vs 10 of 3296 in the control group) and 97.8% (95% confidence interval = 87.1% to 99.9%, 1 of 3240 vs 45 of 3246), respectively. The side effects were mild. No vaccine-related serious adverse events were noted. Robust antibody responses for both types were induced and persisted for at least 42 months.
Conclusions
The E coli-produced HPV-16/18 vaccine is well tolerated and highly efficacious against HPV-16/18–associated high-grade genital lesions and persistent infection in women.
Abstract
Background
Adding radiotherapy (RT) to systemic therapy improves progression-free survival (PFS) and overall survival (OS) in oligometastatic non-small cell lung cancer (NSCLC). Whether ...these findings translate to epidermal growth factor receptor (EGFR)–mutated NSCLC remains unknown. The SINDAS trial (NCT02893332) evaluated first-line tyrosine kinase inhibitor (TKI) therapy for EGFR-mutated synchronous oligometastatic NSCLC and randomized to upfront RT vs no RT; we now report the prespecified interim analysis at 68% accrual.
Methods
Inclusion criteria were biopsy-proven EGFR-mutated adenocarcinoma (per amplification refractory mutation system or next generation sequencing), with synchronous (newly diagnosed, treatment naïve) oligometastatic (≤5 metastases; ≤2 lesions in any one organ) NSCLC without brain metastases. All patients received a first-generation TKI (gefitinib, erlotinib, or icotinib), and randomization was between no RT vs RT (25-40 Gy in 5 fractions depending on tumor size and location) to all metastases and the primary tumor/involved regional lymphatics. The primary endpoint (intention to treat) was PFS. Secondary endpoints included OS and toxicities. All statistical tests were 2-sided.
Results
A total of 133 patients (n = 65 TKI only, n = 68 TKI with RT) were enrolled (2016-2019). The median follow-up was 23.6 months. The respective median PFS was 12.5 months vs 20.2 months (P < .001), and the median OS was 17.4 months vs 25.5 months (P < .001) for TKI only vs TKI with RT. Treatment yielded no grade 5 events and a 6% rate of symptomatic grade 3-4 pneumonitis in the TKI with RT arm. Based on the efficacy results of this prespecified interim analysis, the ethics committee recommended premature cessation of this trial.
Conclusions
As compared with a first-line TKI alone, addition of upfront local therapy using RT statistically significantly improved PFS and OS for EGFR-mutated NSCLC.
Summary Background A vaccine for enterovirus 71 (EV71) is needed to address the high burden of disease associated with infection. We assessed the efficacy, safety, immunogenicity, antibody ...persistence, and immunological correlates of an inactivated alum-adjuvant EV71 vaccine. Methods We did a randomised, double-blind, placebo-controlled, phase 3 trial. Healthy children aged 6–35 months from four centres in China were randomly assigned (1:1) to receive vaccine or alum-adjuvant placebo at day 0 and 28, according to a randomisation list (block size 30) generated by an independent statistician. Investigators and participants and their guardians were masked to the assignment. Primary endpoints were EV71-associated hand, foot, and mouth disease (HFMD) and EV71-associated disease during the surveillance period from day 56 to month 14, analysed in the per-protocol population. This study is registered with ClinicalTrials.gov , number NCT01508247. Findings 10 245 participants were enrolled and assigned: 5120 to vaccine versus 5125 to placebo. 4907 (with three cases of EV71-associated HFMD and eight cases of EV71-associated disease) versus 4939 (with 30 cases of EV71-associated HFMD and 41 cases of EV71-associated disease) were included in the primary efficacy analysis. Vaccine efficacy was 90·0% (95% CI 67·1–96·9) against EV71-associated HFMD (p=0·0001) and 80·4% (95% CI 58·2–90·8) against EV71-associated disease (p<0·0001). Serious adverse events were reported by 62 of 5117 (1·2%) participants in the vaccine group versus 75 of 5123 (1·5%) in the placebo group (p=0·27). Adverse events occurred in 3644 (71·2%) versus 3603 (70·3%; p=0·33). Interpretation EV71 vaccine provides high efficacy, satisfactory safety, and sustained immunogenicity. Funding China's 12–5 National Major Infectious Disease Program, Beijing Vigoo Biological.
This Escherichia coli-produced bivalent HPV 16 and 18 vaccine was well tolerated and effective against HPV 16 and 18 associated high-grade genital lesions and persistent infection in interim analysis ...of this phase 3 trial. We now report data on long-term efficacy and safety after 66 months of follow-up.
This phase 3, double-blind, randomised, controlled trial was done in five study sites in China. Eligible participants were women aged 18–45 years, with intact cervix and 1–4 lifetime sexual partners. Women who were pregnant or breastfeeding, had chronic disease or immunodeficiency, or had HPV vaccination history were excluded. Women were stratified by age (18–26 and 27–45 years) and randomly (1:1) allocated by software (block randomisation with 12 codes to a block) to receive three doses of the E coli-produced HPV 16 and 18 vaccine or hepatitis E vaccine (control) and followed-up for 66 months. The primary outcomes were high-grade genital lesions and persistent infection (longer than 6 months) associated with HPV 16 or 18 in the per-protocol susceptible population. This trial was registered with ClinicalTrials.gov, NCT01735006.
Between Nov 22, 2012, and April 1, 2013, 8827 women were assessed for eligibility. 1455 women were excluded, and 7372 women were enrolled and randomly assigned to receive the HPV vaccine (n=3689) or control (n=3683). Vaccine efficacy was 100·0% (95% CI 67·2–100·0) against high-grade genital lesions (0 0% of 3310 participants in the vaccine group and 13 0·4% of 3302 participants in the control group) and 97·3% (89·9–99·7) against persistent infection (2 0·1% of 3262 participants in the vaccine group and 73 2·2% of 3271 participants in the control group) in the per-protocol population. Serious adverse events occurred at a similar rate between vaccine (267 7·2% of 3691 participants) and control groups (290 7·9% of 3681); none were considered related to vaccination.
The E coli-produced HPV 16 and 18 vaccine was well tolerated and highly efficacious against HPV 16 and 18 associated high-grade genital lesions and persistent infection and would supplement the global HPV vaccine availability and accessibility for cervical cancer prevention.
National Natural Science Foundation of China, National Key R&D Program of China, Fujian Provincial Project, Fundamental Funds for the Central Universities, Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences, and Xiamen Innovax.
Neural circuits that control aversion are essential for motivational regulation and survival in animals. The nucleus accumbens (NAc) plays an important role in predicting aversive events and ...translating motivations into actions. However, the NAc circuits that mediate aversive behaviors remain elusive. Here, we report that tachykinin precursor 1 (Tac1) neurons in the NAc medial shell regulate avoidance responses to aversive stimuli. We show that NAc
neurons project to the lateral hypothalamic area (LH) and that the NAc
→LH pathway contributes to avoidance responses. Moreover, the medial prefrontal cortex (mPFC) sends excitatory inputs to the NAc, and this circuit is involved in the regulation of avoidance responses to aversive stimuli. Overall, our study reveals a discrete NAc Tac1 circuit that senses aversive stimuli and drives avoidance behaviors.
N-Substituted derivatives of 1,4-dideoxy-1,4-imino-d-mannitol (DIM), the pyrrolidine core of swainsonine, have been synthesized efficiently and stereoselectively from d-mannose with ...2,3:5,6-di-O-isopropylidene DIM (10) as a key intermediate. These N-substituted derivatives include N-alkylated, N-alkenylated, N-hydroxyalkylated and N-aralkylated DIMs with the carbon number of the alkyl chain ranging from one to nine. The obtained 33 N-substituted DIM derivatives were assayed against various glycosidases, which allowed a systematic evaluation of their glycosidase inhibition profiles. Though N-substitution of DIM decreased their α-mannosidase inhibitory activities, some of the derivatives showed significant inhibition of other glycosidases.
Eucalyptus trees have been widely planted in China as commercial timber, which has caused severe soil erosion and water deficiency. Near‐natural management by mixing eucalyptus with nitrogen‐fixing ...tree species has been used in plantations to alleviate these problems. In the present study, we investigated the changes in soil microbial community and function in eucalyptus plantations mixed with nitrogen‐fixing trees and with different rotation histories (first and second generation) using Illumina MiSeq. of 16S rRNA gene, coupled with Functional Annotation of Prokaryotic Taxa (FAPROTAX) and Quantitative Microbial Element Cycling (QMEC) analyses.
Both management systems (mixed with nitrogen‐fixing trees and with different rotating time) increased the soil bacterial α‐diversity.
The plantations with different management histories formed different bacterial communities and potential functional structures. Mixing with nitrogen‐fixing trees increased the abundance of Actinobacteria involved in the nitrogen cycle and the abundance of K‐strategy bacteria (Acidobacteria, Verrucomicrobia, Chloroflexi) in both first‐ and second‐generation plantations.
Functionally, the expression of nitrogen‐fixing (nifH) and nitrification genes (amoA1 and hao) increased and that of denitrification genes (nirk2, nirk3, nirS1 and nosZ2) decreased in plantations mixed with nitrogen‐fixing trees. The soil pH, soil water content and bacterial biomass were the key factors driving bacteria community and functional structures. The strategy of mixing eucalyptus with nitrogen‐fixing trees can increase the efficiency of nitrogen cycling by accelerating the nitrogen‐fixing and nitrifying process while inhibiting the denitrifying process.
The results highlight the importance of mixing eucalyptus with nitrogen‐fixing trees for soil microbes and provide useful information on the management of eucalyptus plantations in the future.
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An ionic liquid‐based headspace in‐tube liquid‐phase microextraction (IL‐HS‐ITLPME) in‐line coupled with CE is proposed. The method is capable of quantifying trace amounts of phenols in environmental ...water samples. In the newly developed method, simply by placing a capillary injected with ionic liquids (IL) in the HS above the aqueous sample, volatile phenols were extracted into the IL acceptor phase in the capillary. After extraction, electrophoresis of the phenols in the capillary was carried out. Extraction parameters such as the extraction time, extraction temperature, ionic strength, volume of the sample solution, and IL types were systematically investigated. Under the optimized conditions, enrichment factors for four phenols were from 1510 to 1985. The proposed method provided a good linearity, low limits of detection (below 5.0 ng/mL), and good repeatability of the extractions (RSDs below 6.7%, n = 6). This method was then utilized to analyze two real environmental samples of Xiaoxi Lake and tap water, obtaining acceptable recoveries and precisions. Compared with the usual HS‐ITLPME for CE, IL‐HS‐ITLPME‐CE is a simple, low cost, fast, and environmentally friendly preconcentration technique.
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