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《Vaccine》2022,40(30):4017-4025
Since 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection resulting in the coronavirus disease 2019 (COVID-19) has afflicted hundreds of millions of people in a worldwide pandemic. Several safe and effective COVID-19 vaccines are now available. However, the rapid emergence of variants and risk of viral escape from vaccine-induced immunity emphasize the need to develop broadly protective vaccines. A recombinant plant-derived virus-like particle vaccine for the ancestral COVID-19 (CoVLP) recently authorized by Canadian Health Authorities and a modified CoVLP.B1351 targeting the B.1.351 variant (both formulated with the adjuvant AS03) were assessed in homologous and heterologous prime-boost regimen in mice. Both strategies induced strong and broadly cross-reactive neutralizing antibody (NAb) responses against several Variants of Concern (VOCs), including B.1.351/Beta, B.1.1.7/Alpha, P.1/Gamma, B.1.617.2/Delta and B.1.1.529/Omicron strains. The neutralizing antibody (NAb) response was robust with both primary vaccination strategies and tended to be higher for almost all VOCs following the heterologous prime-boost regimen. 相似文献
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《Vaccine》2015,33(45):6078-6084
BackgroundWe conducted a phase I clinical trial of a cell culture-derived AS03-adjuvanted influenza vaccine containing HA antigen (A/Indonesia/05/2005(H5N1)/PR8-IBCDC-RG2) derived from EB66 cells (KD-295).MethodsHealthy male adult volunteers (20–40 years old, N = 60) enrolled in the study were divided into 3 groups, the MA group (3.8 μg of HA + AS03), HA group (7.5 μg of HA + AS03), and 1/2 MA group (half the volume of the MA group), and received KD-295 intramuscularly twice with a 21-day interval. After administration of KD-295, adverse events, clinical laboratory parameters, and immune response to the vaccine strain and heterologous virus strains were evaluated.ResultsNo severe adverse events leading to discontinuation of vaccine administration occurred. The vaccine was well-tolerated. There was no dose dependency in the rate, timing, or duration of the adverse events. Immunogenicity of the vaccines was evaluated by HI (hemagglutination inhibition) assay, which confirmed that the antibody response to the vaccine strain and heterologous strain in all groups met the three criteria for immunogenicity described in the Japanese guidelines for development of a pandemic prototype vaccine. We also measured the neutralizing antibody titers against several virus strains, and confirmed a significant rise in antibody levels to both the vaccine strain and heterologous strains.ConclusionThe EB66-derived H5N1 influenza vaccine adjuvanted with AS03 elicited a broad cross-reactive antibody response among H5N1 strains with acceptable reactogenicity. Therefore, KD-295 can be considered a useful pandemic and pre-pandemic influenza vaccine candidate. 相似文献
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Co-existence of Asperger syndrome (AS) and non-verbal learning disability (NLD) has been proposed based on the observation that people with AS tend to have significantly higher verbal than performance IQ (VIQ>PIQ by ≥15 points), one of the core features of NLD. In the present study we examined neuropsychological and social adaptive profiles with “non-verbal learning problems” associated with NLD in a group of individuals with AS followed from childhood into early adult life. The group was divided into three subgroups: (i) persistent NLD (P-NLD), i.e. NLD (VIQ>PIQ) both in childhood and early adulthood occasions, (ii) childhood NLD (CO-NLD), i.e. NLD (VIQ>PIQ) only at original diagnosis, or (iii) No NLD (VIQ>PIQ) ever (NO-NLD). All three subgroups were followed prospectively from childhood into adolescence and young adult life. One in four to one in five of the whole group of males with AS had P-NLD. The P-NLD subgroup had poorer neuropsychological outcome in early adult life than did those with CO-NLD and those with NO-NLD. There were no unequivocal markers in early childhood that predicted subgroup status in early adult life, but early motor delay and a history of early speech-language problems tended to be associated with P-NLD. 相似文献
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Qingyuan Zhu Jun Chen Jun Xiong Lunbin Lu Siyuan Zhu Zhiying Zhong Genhua Tang Xingchen Zhou Han Guo 《Medicine》2021,100(15)
Background:Ankylosing spondylitis is a complex and progressive autoimmune inflammatory disease with a worldwide prevalence ranging up to 0.9%. Several systematic reviews and meta-analyses of traditional Chinese medicine alternative therapies, such as acupuncture or moxibustion, have demonstrated the effectiveness of moxibustion and acupuncture in the treatment of ankylosing spondylitis. However, there is no relevant literature to comprehensively evaluate the evidence. The purpose of this overview is to synthesize and evaluate the reliability of evidence generated in the systematic review (SR) and meta-analysis of moxibustion and acupuncture as a primary or complementary therapy for patients with ankylosing spondylitis.Methods:PubMed, EMBASE, the Cochrane Central Register of Controlled Trials, Chinese National Knowledge Infrastructure, Chinese VIP Information, Wanfang Database, and Chinese Biomedical Literature Database were searched for systematic reviews and meta-analysis that review the efficacy of acupuncture or moxibustion as the primary treatment for patients with Ankylosing Spondylitis. The literature published before August 2020 will be selected. Additionally, the relevant SRs and meta-analyses that unpublished or ongoing will be searched in PROSPERO and INPLASY. The methodological guidelines for overviews will be used to review and extract data by 2 reviewers, and their will do it independently. Methodology quality will be analyzed by the assessment of multiple systematic reviews-2and the risk of bias by POBIS. For the included studies, we will adopt the following results as primary evaluation indicators: effective rate, visual analogue scale and bath AS disease activity index. Reviewers will assess the certainty of evidence by Grading of Recommendations Assessment, Development and Evaluation.Results:The results will be published in a peer-reviewed journal.Conclusion:This overview will provide comprehensive evidence of moxibustion and acupuncture for patients with Ankylosing Spondylitis. 相似文献
18.
Kang H. Zheng Sotirios Tsimikas Tania Pawade Jeffrey Kroon William S.A. Jenkins Mhairi K. Doris Audrey C. White Nyanza K.L.M. Timmers Jesper Hjortnaes Maximillian A. Rogers Elena Aikawa Benoit J. Arsenault Joseph L. Witztum David E. Newby Marlys L. Koschinsky Zahi A. Fayad Erik S.G. Stroes S. Matthijs Boekholdt Marc R. Dweck 《Journal of the American College of Cardiology》2019,73(17):2150-2162
Background
Lipoprotein(a) [Lp(a)], a major carrier of oxidized phospholipids (OxPL), is associated with an increased incidence of aortic stenosis (AS). However, it remains unclear whether elevated Lp(a) and OxPL drive disease progression and are therefore targets for therapeutic intervention.Objectives
This study investigated whether Lp(a) and OxPL on apolipoprotein B-100 (OxPL-apoB) levels are associated with disease activity, disease progression, and clinical events in AS patients, along with the mechanisms underlying any associations.Methods
This study combined 2 prospective cohorts and measured Lp(a) and OxPL-apoB levels in patients with AS (Vmax >2.0 m/s), who underwent baseline 18F-sodium fluoride (18F-NaF) positron emission tomography (PET), repeat computed tomography calcium scoring, and repeat echocardiography. In vitro studies investigated the effects of Lp(a) and OxPL on valvular interstitial cells.Results
Overall, 145 patients were studied (68% men; age 70.3 ± 9.9 years). On baseline positron emission tomography, patients in the top Lp(a) tertile had increased valve calcification activity compared with those in lower tertiles (n = 79; 18F-NaF tissue-to-background ratio of the most diseased segment: 2.16 vs. 1.97; p = 0.043). During follow-up, patients in the top Lp(a) tertile had increased progression of valvular computed tomography calcium score (n = 51; 309 AU/year [interquartile range: 142 to 483 AU/year] vs. 93 AU/year [interquartile range: 56 to 296 AU/year; p = 0.015), faster hemodynamic progression on echocardiography (n = 129; 0.23 ± 0.20 m/s/year vs. 0.14 ± 0.20 m/s/year] p = 0.019), and increased risk for aortic valve replacement and death (n = 145; hazard ratio: 1.87; 95% CI: 1.13 to 3.08; p = 0.014), compared with lower tertiles. Similar results were noted with OxPL-apoB. In vitro, Lp(a) induced osteogenic differentiation of valvular interstitial cells, mediated by OxPL and inhibited with the E06 monoclonal antibody against OxPL.Conclusions
In patients with AS, Lp(a) and OxPL drive valve calcification and disease progression. These findings suggest lowering Lp(a) or inactivating OxPL may slow AS progression and provide a rationale for clinical trials to test this hypothesis. 相似文献19.
Background/Objectives
Due to its rarity, epidermoid cyst in intrapancreatic accessory spleen (ECIPAS) is still a diagnostic dilemma during clinical practice. The aim of this review was to summarize the epidemiologic features and management of ECIPAS.Methods
MEDLINE and EMBASE were searched for English articles reporting on ECIPAS up to April 30th, 2018 following the methodology suggested by the PRISMA guidelines. Categorical variables were reported as frequency and percentage. Continuous variables were reported as median (range).Results
A total of 56 patients from 47 full articles were included for the final data synthesis. More than half of the ECIPASs (59%) were found incidentally. The female/male ratio was 1.33. ECIPAS is typically a single mono-/multi-lobular cystic lesions in the pancreatic tail with thickened cystic wall or various amount of solid component which had identical density/signal to the spleen on imaging examinations. The cyst is filled with serous or non-serous fluid. Recognition of the surrounding ectopic splenic tissue is the key point to diagnose ECIPAS. However, no preoperative examination was able to make a definite diagnosis. Almost all the patients (96%) received surgical treatment, due to the suspicion of pancreatic malignant or potentially malignant cystic tumor, especially mucinous cystic neoplasm (MCN).Conclusions
Although seldom encountered, ECIPAS should be considered as a differential diagnosis for pancreatic cystic lesions, especially when solid component was detected. As a benign disease, unnecessary surgery should be avoided. Because it is difficult to make a definite diagnosis preoperatively by one single examination, multiple modalities may be required. 相似文献20.
《Vaccine》2015,33(42):5578-5587
Liposomes have shown promise as constituents of adjuvant formulations in vaccines to parasitic and viral diseases. A particular type of liposomal construct, referred to as Army Liposome Formulation (ALF), containing neutral and anionic saturated phospholipids, cholesterol, and monophosphoryl lipid A (MPLA), has been used as an adjuvant for many years. Here we investigated the effects of physical and chemical changes of ALF liposomes on adjuvanted immune responses to CN54 gp140, a recombinant HIV-1 envelope protein. While holding the total amounts of liposomal MPLA and the gp140 antigen constant, different liposome sizes and liposomal MPLA:phospholipid molar ratios, and the effect of adding QS21 to the liposomes were compared for inducing immune responses to the gp140. For liposomes lacking QS21, higher titers of IgG binding antibodies to gp140 were induced by small unilamellar vesicle (SUV) rather than by large multilamellar vesicle (MLV) liposomes, and the highest titers were obtained with SUV having the MPLA:phospholipid ratio of 1:5.6. ALF plus QS21 (ALFQ) liposomes induced the same maximal binding antibody titers regardless of the MPLA:phospholipid ratio. ALF MLV liposomes induced mainly IgG1 and very low IgG2a antibodies, while ALF SUV liposomes induced IgG1 ≥ IgG2a > IgG2b antibodies. Liposomes containing QS21 induced IgG1 > IgG2a > IgG2b > IgG3 antibodies. ELISPOT analysis of splenocytes from immunized mice revealed that ALF liposomes induced low levels of IFN-γ, but ALFQ induced high levels. ALF and ALFQ liposomes each induced approximately equivalent high levels of IL-4. Based on antibody subtypes and cytokine secretion, we conclude that ALF liposomes predominantly stimulate Th2, while ALFQ strongly induces both Th1 and Th2 immunity. When CN54 gp140 was adjuvanted with either ALF or ALFQ liposomes, antibodies were induced that neutralized two HIV-1 tier 1 clade C strain pseudoviruses. 相似文献