Human influenza A

人类甲型流感
  • 文章类型: Journal Article
    甲型流感有两个血凝素组,与群体之间相比,内部对再感染的交叉免疫力更强。这里,我们探讨了这种异质性对拟议的交叉保护性流感疫苗的影响,这些疫苗可能提供广泛的,但不是普遍的,保护。虽然人类甲型流感疫苗的开发目标是提供跨群体保护,目前发展阶段的疫苗可能比非目标群体对目标群体提供更好的保护。为了评估疫苗配方和策略,我们提出了一个新的观点:疫苗群体水平目标产品概况(PTPP)。在这个视角下,我们使用动态模型来量化未来甲型流感疫苗的流行病学影响,作为其特性的函数.我们的结果表明,天然免疫和疫苗诱导免疫的相互作用可以强烈影响季节性亚型动态。广泛保护性的二价疫苗可以降低两组的发病率,并以足够的疫苗接种覆盖率实现消除。然而,低疫苗接种率的单价疫苗可以允许非目标人群在疫苗提供比自然感染更弱的免疫力时复活。此外,作为大流行模拟的代理,我们分析了一种逃避自然免疫的变种的入侵。我们发现,未来的疫苗在足够高的疫苗接种率下提供足够广泛和长寿命的跨群体保护,可以防止大流行的出现并减轻大流行的负担。这项研究强调,除了有效性之外,对于未来的人类甲型流感疫苗,应在流行病学知情的TPPs中考虑宽度和持续时间。
    Influenza A has two hemagglutinin groups, with stronger cross-immunity to reinfection within than between groups. Here, we explore the implications of this heterogeneity for proposed cross-protective influenza vaccines that may offer broad, but not universal, protection. While the development goal for the breadth of human influenza A vaccine is to provide cross-group protection, vaccines in current development stages may provide better protection against target groups than non-target groups. To evaluate vaccine formulation and strategies, we propose a novel perspective: a vaccine population-level target product profile (PTPP). Under this perspective, we use dynamical models to quantify the epidemiological impacts of future influenza A vaccines as a function of their properties. Our results show that the interplay of natural and vaccine-induced immunity could strongly affect seasonal subtype dynamics. A broadly protective bivalent vaccine could lower the incidence of both groups and achieve elimination with sufficient vaccination coverage. However, a univalent vaccine at low vaccination rates could permit a resurgence of the non-target group when the vaccine provides weaker immunity than natural infection. Moreover, as a proxy for pandemic simulation, we analyze the invasion of a variant that evades natural immunity. We find that a future vaccine providing sufficiently broad and long-lived cross-group protection at a sufficiently high vaccination rate, could prevent pandemic emergence and lower the pandemic burden. This study highlights that as well as effectiveness, breadth and duration should be considered in epidemiologically informed TPPs for future human influenza A vaccines.
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  • 文章类型: Journal Article
    与严重急性呼吸道综合症相关的冠状病毒-2(SARS-CoV-2)和流感病毒以前所未有的速度在世界范围内传播。尽管有多种疫苗,SARS-CoV-2和流感的新变种引起了显着的发病机制。开发治疗SARS-CoV-2和流感的有效抗病毒药物仍然是当务之急。抑制病毒细胞表面附着是阻止病毒感染的早期有效手段。唾液酸糖缀合物,在人类细胞膜表面,作为甲型流感病毒的宿主细胞受体发挥重要作用,9-O-乙酰-唾液酸化糖缀合物是MERS的受体,HKU1和牛冠状病毒。我们在室温下通过点击化学简洁地设计和合成了多价6'-唾液酸乳糖共轭聚酰胺胺树枝状聚合物。这些树枝状聚合物衍生物在水溶液中具有良好的溶解性和稳定性。SPR,一种实时分析生物分子相互作用的定量方法,通过仅使用200微克的每种树枝状聚合物来研究我们的树枝状聚合物衍生物的结合亲和力。三个SARS-CoV-2S蛋白受体结合域(野生型和两个Omicron突变体)与多价9-O-乙酰基-6'-唾液酸乳糖缀合的和6'-唾液酸乳糖缀合的树枝状聚合物结合到单个H3N2甲型流感病毒HA蛋白(A/HongKong/1/1968),SPR研究结果提示其具有潜在的抗病毒活性.
    Severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) and influenza viruses have spread around the world at an unprecedented rate. Despite multiple vaccines, new variants of SARS-CoV-2 and influenza have caused a remarkable level of pathogenesis. The development of effective antiviral drugs to treat SARS-CoV-2 and influenza remains a high priority. Inhibiting viral cell surface attachment represents an early and efficient means to block virus infection. Sialyl glycoconjugates, on the surface of human cell membranes, play an important role as host cell receptors for influenza A virus and 9-O-acetyl-sialylated glycoconjugates are receptors for MERS, HKU1 and bovine coronaviruses. We designed and synthesized multivalent 6\'-sialyllactose-counjugated polyamidoamine dendrimers through click chemistry at room temperature concisely. These dendrimer derivatives have good solubility and stability in aqueous solutions. SPR, a real-time analysis quantitative method for of biomolecular interactions, was used to study the binding affinities of our dendrimer derivatives by utilizing only 200 micrograms of each dendrimer. Three SARS-CoV-2 S-protein receptor binding domain (wild type and two Omicron mutants) bound to multivalent 9-O-acetyl-6\'-sialyllactose-counjugated and 6\'-sialyllactose-counjugated dendrimers bound to a single H3N2 influenza A virus\'s HA protein (A/Hong Kong/1/1968), the SPR study results suggest their potential anti-viral activities.
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  • 文章类型: Journal Article
    BACKGROUND: Through the comparison of the demographic, epidemiological, and clinical characteristics of hospital human influenza (influenza A (H1N1) pdm09, H3N2, and B)-related and hospitalized avian-origin influenza A (H7N9)-related viral pneumonia patients, find the different between them.
    METHODS: A retrospective study was conducted in hospitalized influenza-related viral pneumonia patients.
    RESULTS: Human influenza A-related patients in the 35-49-year-old group were more than those with B pneumonia patients (p = 0.027), and relatively less in the ≥ 65-year-old group than B pneumonia patients (p = 0.079). The proportion of comorbid condition to human influenza A pneumonia was 58%, lower than B pneumonia and H7N9 pneumonia patients (78% vs. 77.8%; p = 0.013). The proportion of invasive mechanical ventilation (IMV), lymphocytopenia, elevated lactate dehydrogenase to hospitalized human influenza A-related viral pneumonia patients was higher than B pneumonia patients (p < 0.05), but lower than H7N9 pneumonia patients (p < 0.05). In the multivariate analysis, pulmonary consolidation (odds ratio (OR): 13.67; 95% confidence interval (CI) 1.54-121.12; p = 0.019) and positive bacterial culture (sputum) (OR: 7.71; 95% CI 2.48-24.03; p < 0.001) were independently associated with IMV, while shock (OR: 13.16; 95% CI 2.06-84.07; p = 0.006), white blood cell count > 10,000/mm3 (OR: 7.22; 95% CI 1.47-35.58; p = 0.015) and positive bacterial culture(blood or sputum) (OR: 6.27; 95% CI 1.36-28.85; p = 0.018) were independently associated with death in the three types hospitalized influenza-related viral pneumonia patients.
    CONCLUSIONS: Hospital influenza B-related viral pneumonia mainly affects the elderly and people with underlying diseases, while human influenza A pneumonia mainly affects the young adults; however, the mortality was similar. The hospitalized human influenza A-related viral pneumonia patients was severer than B pneumonia patients, but milder than H7N9 pneumonia patients. Pulmonary consolidation and positive bacterial culture (sputum) were independently associated with IMV, while shock, white blood cell count > 10,000/mm3, and positive bacterial culture (blood or sputum) were independently associated with death to three types hospitalized influenza-related viral pneumonia patients.
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