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81.
《Vaccine》2019,37(22):2952-2959
CD8+ T cells are known to control infections, but their role in preventing latent infection from establishing has not been thoroughly investigated.We hypothesized that a potent CD8+ T cell response patrolling the mucosal viral entry points could kill the first infected cells and thereby abrogate the infection before latency is established.To investigate this, replication deficient adenovirus serotype 5 vectors encoding murine γ-herpesvirus-68 CD8+ T cell epitopes linked to the T cell adjuvant Invariant chain, were developed. We show that intranasal vaccination of mice reduces the risk of establishment of latent infection from multiple intranasal ID50 challenges with murine γ-herpesvirus-68 by 81% per exposure at 14 days post vaccination. Protection waned over time, but immune responses were extended by heterologous prime-boost vaccination applied simultaneously intramuscularly and intranasally, and animals vaccinated 66 days prior to challenge showed a strong trend of long-term protection.Our data provides evidence that CD8+ T cells are able to protect against establishment of latent infection. Although the protective efficacy is difficult to maintain over time, this proof-of-concept study suggests a role for a CD8+ T cell arm in future vaccine strategies against latent human viral infections caused by pathogens such as HIV and multiple herpes virus. 相似文献
82.
《Vaccine》2019,37(37):5535-5543
Recent studies have suggested that among those receiving seasonal influenza vaccine (SIV), reduced immunogenicity is observed in recently vaccinated (RV; within the past season or 2) persons when compared with those not recently vaccinated (NRV). We performed a meta-analysis to assess the effect of recent immunization with SIV on serum H5 hemagglutination inhibition (HAI) antibody responses after influenza A/H5N1 vaccination using data from a series of randomized controlled trials. The primary outcome was seroconversion measured by HAI assays following receipt of 2 doses of H5N1 vaccine. The geometric mean titer (GMT) of serum HAI antibody after vaccination was the secondary outcome. Analyses were performed using propensity score (PS) matching. The PS for each individual in the meta-analysis cohort was calculated using logistic regression and covariates included age, gender, race, antigen dose, adjuvant, statin use and vaccine manufacturer. 2015 subjects enrolled in 7 clinical trials were eligible for inclusion in the meta-analysis cohort; among these, 915 (45%) were RV. 901 RV subjects were matched (1:1) with replacement to a subject who was NRV. Subjects who received SIV within the previous season were significantly less likely to seroconvert following H5N1 vaccination (adjusted odds ratio 0.76; 95%CI 0.60–0.96; p = 0.024), and the GMT was 18% higher among NRV subjects (GM ratio of HAI antibody 1.18; 95%CI 1.04–1.33; p = 0.008). Further work is needed to better define the effects of, and mechanisms contributing to, reduced immune responses to H5N1 vaccine among RV subjects. 相似文献
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Understanding why persons with human immunodeficiency virus (HIV) have accelerated atherosclerosis and its sequelae, including coronary artery disease (CAD) and myocardial infarction, is necessary to provide appropriate care to a large and aging population with HIV. In this review, we delineate the diverse pathophysiologies underlying HIV-associated CAD and discuss how these are implicated in the clinical manifestations of CAD among persons with HIV. Several factors contribute to HIV-associated CAD, with chronic inflammation and immune activation likely representing the primary drivers. Increased monocyte activation, inflammation, and hyperlipidemia present in chronic HIV infection also mirror the pathophysiology of plaque rupture. Furthermore, mechanisms central to plaque erosion, such as activation of toll-like receptor 2 and formation of neutrophil extracellular traps, are also abundant in HIV. In addition to inflammation and immune activation in general, persons with HIV have a higher prevalence than uninfected persons of traditional cardiovascular risk factors, including dyslipidemia, hypertension, insulin resistance, and tobacco use. Antiretroviral therapies, although clearly necessary for HIV treatment and survival, have had varied effects on CAD, but newer generation regimens have reduced cardiovascular toxicities. From a clinical standpoint, this mix of risk factors is implicated in earlier CAD among persons with HIV than uninfected persons; whether the distribution and underlying plaque content of CAD for persons with HIV differs considerably from uninfected persons has not been definitively studied. Furthermore, the role of cardiovascular risk estimators in HIV remains unclear, as does the role of traditional and emerging therapies; no trials of CAD therapies powered to detect clinical events have been completed among persons with HIV. 相似文献
87.
Binaya Basyal Harish Jarrett Christopher F. Barnett 《The Canadian journal of cardiology》2019,35(3):288-298
Human immunodeficiency virus–associated pulmonary arterial hypertension (HIV-PAH) is important to recognize given its association with significant morbidity and mortality. With the introduction of antiretroviral therapy, the focus of disease management has largely shifted from treating immunodeficiency-related opportunistic infections to managing chronic cardiopulmonary complications. Symptoms are nonspecific, and a high index of clinical suspicion is needed to avoid significant delay in the diagnosis of HIV-PAH. Although several viral proteins have been implicated in the pathogenesis of HIV-PAH, the exact mechanism remains uncertain. Further studies are needed to elucidate precise pathogenic mechanisms, early diagnostic tools, and novel therapeutic targets to improve prognosis of this severe complication. 相似文献
88.
Conall T. Morgan Angela Tang Chun-Po Fan Fraser Golding Cedric Manlhiot Glen van Arsdell Osami Honjo Edgar Jaeggi 《The Canadian journal of cardiology》2019,35(4):446-452
Background
Common arterial trunk (CAT) is a rare anomaly with a spectrum of pathology. We sought to identify current trends and factors associated with postnatal outcomes.Methods
This was a single-centre review including 153 live births with planned surgery. Patients were analyzed as 2 cohorts based on era of CAT diagnosis (1990 to 1999 vs 2000 to 2014) and complexity of disease (simple vs complex). “Complex” required the association with significant aortic arch obstruction, truncal valve (TV) stenosis/regurgitation, and/or branch pulmonary artery (PA) hypoplasia, respectively.Results
Sixteen (10%) died preoperatively, and this outcome was associated with significant TV stenosis (odds ratio [OR] 4.55; P = 0.01) and regurgitation (OR 3.17; P = 0.04); 130 (95%) of 137 operated infants underwent primary complete repair. Their survival rates to 1 year improved from 54% to 85% after 2000, although this outcome remained substantially lower for cases with a complex vs simple CAT repair (76% vs 95%; OR 6.46; P = 0.006). Other risk factors associated with decreased 1-year survival included diagnosis before 2000 (OR 4.48; P = 0.038) and a lower birth weight (OR 8.0 per kg weight; P = 0.001). Finally, of 93 survivors beyond year 1 of life, 76 (82%) had undergone a total of 224 reinterventions. Only 15 (16%) were alive without any surgical or catheter-based reintervention at study end.Conclusions
Despite recent surgical improvements, postnatal mortality continues to be substantial if CAT is complicated by significant pathology of the TV, aortic arch, or branch PAs. Reoperations and catheter interventions are eventualities for most patients during childhood. 相似文献89.
K. Miura S. Yamaoka K. Arizono S. Ohba T. Koga T. Kawasaki N. Yoshida I. Asahina 《The British journal of oral & maxillofacial surgery》2019,57(6):529-535
Our aim was to evaluate the long-term skeletal stability of the mandible in 21 patients after orthognathic surgery with physiological positioning. The measurement points SNB, B point (X, Y), Pog (X, Y), and the angle of the ramus were measured on cephalometric photographs to assess skeletal stability preoperatively, immediately after operation, and one and two years postoperatively. In addition, we evaluated the clinical symptoms of disorders of the temporomandibular joint (TMJ). The analysis of the cephalometric photographs showed that SNB, B point X, and Pog X showed no significant differences among the postoperative time points. On the other hand, B point Y and Pog Y showed no significant differences throughout the study period. We compared the angle of the ramus before operation and two years postoperatively, and no significant difference was found. In addition, no cases showed any pathological symptoms of disorders of the TMJ two years postoperatively. The long-term stability after orthognathic surgery with physiological positioning was confirmed, and it seems to be a reliable orthognathic treatment in patients with mandibular prognathism. 相似文献
90.