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（由申请方提供）：肺炎链球菌是肺炎、脑膜炎和败血症等危及生命的疾病的主要原因。世界卫生组织估计，每年至少有160万人死于肺炎球菌感染。然而，肺炎球菌感染可以显着减少疫苗，诱导抗体（抗体）对肺炎球菌多糖（PPS）胶囊反应。IgG同种型的PPS特异性抗体可提供最实质性的保护，防止生命威胁侵袭性疾病。因此，引发PPS特异性IgG是疫苗接种的主要目标。目前的建议源于我们惊人的初步数据，表明小鼠和灵长类动物的呼吸道病毒感染可以显着减少IgG的数量，但增加伊加，产生于对病毒感染前几周给予的多糖抗原的反应。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抗S.肺炎和其他被包裹的细菌。我们的目标是检验这一假设，并确定病毒感染诱导的信号，调节多糖特异性抗体反应。此外，我们还提出了一个新的假设，即病毒感染诱导Ps特异性IG β分泌细胞进行二级类别转换重组。从这些研究中获得的结果预计将提供有关病毒诱导因素和机制的重要线索，这些因素和机制涉及将多糖特异性IgG反应转变为伊加反应，以及这种调节可能对人类中基于多糖的疫苗效力产生的生理影响。