Viral Modulation of Polysaccharide Antibody Responses and Vaccine Efficacy

多糖抗体反应和疫苗功效的病毒调节

• 批准号: 9018144
• 负责人: Karen M Haas
• 金额: $ 19.48万
• 依托单位: WAKE FOREST UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-03-17 至 2018-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9018144
• 关键词: Accounting; Acute; Antibodies; Antibody Formation; Antibody Response; Antigens; Attenuated; B-Lymphocytes; Bacteria; Bone Marrow; Cells; Characteristics; Data; Disease; Employee Strikes; Encapsulated; Exhibits; Goals; Health; Human; Immune system; Immunization; Immunoglobulin A; Immunoglobulin Class Switching; Immunoglobulin G; Immunoglobulin M; Immunoglobulin Switch Recombination; Incidence; Infection; Influenza; Interferon Type I; Knowledge; Lead; Life; Memory B-Lymphocyte; Meningitis; Modeling; Mus; Myxovirus; Neuraminidase; Parainfluenza; Physiological; Plasma Cells; Plasmablast; Play; Pneumococcal Infections; Pneumonia; Polysaccharides; Polyvalent pneumococcal vaccine; Population; Primates; Production; Proteins; Public Health; Research; Respiratory Tract Infections; Role; Sepsis; Serotyping; Serum; Signal Transduction; Streptococcus pneumoniae; T-Lymphocyte; TI 2 Antigens; TNP-ficoll; Testing; Transforming Growth Factor beta; Vaccination; Vaccines; Viral; Viral Respiratory Tract Infection; Viral Vaccines; Virus; Virus Diseases; Work; World Health Organization; base; capsule; clinically relevant; cytokine; improved; influenzavirus; nonhuman primate; novel; parainfluenza virus; pathogen; public health relevance; receptor; respiratory infection virus; respiratory virus; response; self-renewal; stem; vaccine efficacy; vaccine-induced immunity; viral RNA

 DESCRIPTION (provided by applicant): Streptococcus pneumoniae is a major cause of life‑threatening diseases such as pneumonia, meningitis and sepsis. The World Health Organization estimates that at least 1.6 million people die each year from pneumococcal infections. However, pneumococcal infections can be significantly reduced by vaccines that induce antibodies (Abs) reactive against the pneumococcal polysaccharide (PPS) capsule. PPS‑specific Abs of the IgG isotype offers the most substantial protection against life‑threatenin invasive disease. Thus, eliciting PPS‑specific IgG is a major goal of vaccination. The current proposal stems from our striking preliminary data showing that respiratory virus infections in mice and primates can dramatically reduce the quantity of IgG, but increase IgA, produced in response to polysaccharide antigens that were administered several weeks preceding viral infection. We therefore hypothesize that respiratory viral infections may have important physiological consequences for polysaccharide‑based vaccine induced‑protection against S. pneumoniae and other encapsulated bacteria. Our objectives are to test this hypothesis and define the virus infection‑induced signals that modulate polysaccharide‑specific Ab responses. In addition, we propose to test the novel hypothesis that virus infection induces Ps‑specific Ig��secreting cells to undergo secondary class switch recombination. The results obtained from these studies are expected to provide important clues regarding the viral-induced factors and mechanisms involved in shifting polysaccharide‑specific IgG responses to IgA responses, as well as the physiological impact this modulation may have on polysaccharide‑based vaccine efficacy in humans.

 描述（由适用提供）：肺炎链球菌是威胁生命疾病的主要原因，例如肺炎，脑膜炎和脓毒症。世界卫生组织估计，每年至少有160万人死于肺炎球菌感染。但是，影响抗体（ABS）对肺炎球菌多糖（PPS）胶囊的反应性疫苗可显着降低肺炎球菌感染。 IgG同种型的PPS特异性ABS提供了对生命威胁性侵袭性疾病的最实质性保护。这是引起PPS特异性IgG的主要目标。目前的提案步骤来自我们的罢工初步数据，表明小鼠和私人的呼吸病毒感染可以大大减少IgG的数量，但增加了IgA，而IgA则是针对病毒感染前几周施用的多糖抗原而产生的。因此，我们假设呼吸道病毒感染可能对基于多糖的疫苗诱导的肺炎链球菌和其他封装细菌产生重要的物理后果。我们的目标是检验该假设，并定义病毒感染引起的信号，以调节多糖特异性AB反应。此外，我们建议测试新的假设，即病毒感染诱导PS特异性Ig。分泌细胞以进行二级开关重组。预计从这些研究中获得的结果将提供有关病毒诱导的因素和机制的重要线索，这些因素和机制转移了对IgA反应的多糖特异性IgG反应，以及该调节对人类基于多糖的疫苗效率的物理影响。