Systems Analysis Vaccine Responses in Healthy and Hyporesponsive Humans

健康和低反应人类的疫苗反应系统分析

• 批准号: 9113204
• 负责人: Maria Virginia Pascual
• 金额: $ 12.38万
• 依托单位: BAYLOR RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-01 至 2017-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9113204
• 关键词: Adjuvant; Antibody Response; Antigens; Attenuated; Biological Assay; Biological Markers; Blood Cells; CPG-oligonucleotide; Cells; Dendritic Cells; Development; Fluzone; Gene Expression Profile; Genetic; Goals; Health; Helper-Inducer T-Lymphocyte; Hepatitis B Vaccines; Host Defense; Human; Immune; Immune response; Immune system; Immunity; Immunobiology; Immunocompromised Host; Immunology; Individual; Infection; Influenza; Instruction; Knowledge; Lead; Life; Ligands; Medical; Modus; Patients; Pattern recognition receptor; Pneumovax; Population; Population Heterogeneity; Predisposition; Process; Rest; Systems Analysis; Systems Biology; Time; Vaccination; Vaccines; Viral; Virus; aluminum sulfate; cohort; design; healthy volunteer; improved; influenza virus vaccine; monocyte; neutralizing antibody; novel; particle; response; success; tool; vaccine efficacy; vaccine response

DESCRIPTION (provided by applicant): Vaccines represent the major success of immunology and have spared countless numbers of people from infections. Despite this success, we understand little about how effective vaccines stimulate protective immune responses. We surmise that understanding the modus operandi of vaccines in healthy people and understanding their shortcomings by studying hypo-responsive people will permit us to unravel the immunological principles of vaccination. Three vaccines will be studied in great detail: inactivated influenza vaccine and hepatitis B vaccine with either alum as the traditional adjuvant (Engerix) or with CPGoligonucleotide (Heplisav). We surmise that systems biology approaches will permit us to gain a comprehensive view of the immunobiology associated with a potent response to vaccination. This will lead to the identification of biomarker signatures indicative of the quality of vaccine-induced antibody responses. This, in turn, will facilitate the rational design and development of novel improved vaccines. Our preliminary studies performed with 24 healthy volunteers indicate that three commercially available vaccines: Fluzone (influenza), Pneumovax and Engerix alter the blood cell composition and transcriptome in completely different ways. These preliminary results support our proposed strategy. They demonstrate that the different vaccines, which are able to induce protective humoral responses, mobilize different immune effectors. We propose five highly integrated projects which will be supported by seven cores. Our key deliverables will include: i) Increased knowledge on vaccine-induced immune system alterations in dendritic cells, monocytes and T follicular helper cells; ii) Biomarkers of humoral immune responses; iii) An ex vivo assay for prediction of immune response to vaccination; iv) Tools to assess vaccine-activated cells; v) A systems biology analysis of two adjuvants: Alum and CPG-Oligonucleotides; vi) A systems biology analysis of the response to vaccine in patients with altered immune systems; and vii) An Immunochip, or focused microarray, for the assessment of vaccine immune efficacy.

描述（由申请人提供）：疫苗代表了免疫学的重大成功，使无数人免受感染。尽管取得了这一成功，但我们对有效疫苗如何刺激保护性免疫反应知之甚少。我们推测，了解健康人接种疫苗的方式并通过研究反应低下的人了解其缺点将使我们能够阐明疫苗接种的免疫学原理。将详细研究三种疫苗：灭活流感疫苗和乙型肝炎疫苗，以明矾作为传统佐剂 (Engerix) 或以 CPG 寡核苷酸 (Heplisav) 为佐剂。我们推测系统生物学方法将使我们能够全面了解与疫苗接种有效反应相关的免疫生物学。这将导致鉴定表明疫苗诱导的抗体反应质量的生物标志物特征。反过来，这将促进新型改良疫苗的合理设计和开发。我们对 24 名健康志愿者进行的初步研究表明，三种市售疫苗：Fluzone（流感）、Pneumovax 和 Engerix 以完全不同的方式改变血细胞组成和转录组。这些初步结果支持我们提出的策略。他们证明，不同的疫苗能够诱导保护性体液反应，调动不同的免疫效应器。我们提出了五个高度集成的项目，将由七个核心支持。我们的主要成果包括： i) 增加对疫苗诱导的树突状细胞、单核细胞和滤泡辅助 T 细胞免疫系统改变的了解； ii) 体液免疫反应的生物标志物； iii) 预测疫苗接种免疫反应的离体测定； iv) 评估疫苗激活细胞的工具； v) 两种佐剂的系统生物学分析：明矾和 CPG-寡核苷酸； vi) 对免疫系统改变的患者对疫苗的反应进行系统生物学分析； vii) 免疫芯片或聚焦微阵列，用于评估疫苗免疫功效。

项目成果

Innate immune dysfunction is associated with enhanced disease severity in infants with severe respiratory syncytial virus bronchiolitis.

先天免疫功能障碍与患有严重呼吸道合胞病毒细支气管炎的婴儿的疾病严重程度增加有关。

• 发表时间: 2013-02-15
• 作者: Mella, Cesar;Suarez;Lopez, Santiago;Stephens, Julie;Fernandez, Soledad;Hall, Mark W;Ramilo, Octavio;Mejias, Asuncion
• 通讯作者: Mejias, Asuncion

H3N2 influenza virus infection induces broadly reactive hemagglutinin stalk antibodies in humans and mice.

H3N2 流感病毒感染可在人和小鼠体内诱导广泛反应性血凝素柄抗体。

• 发表时间: 2013-04
• 作者: Margine, Irina;Hai, Rong;Albrecht, Randy A;Obermoser, Gerlinde;Harrod, A Carson;Banchereau, Jacques;Palucka, Karolina;García;Palese, Peter;Treanor, John J;Krammer, Florian
• 通讯作者: Krammer, Florian

ICOS(+)PD-1(+)CXCR3(+) T follicular helper cells contribute to the generation of high-avidity antibodies following influenza vaccination.

ICOS( )PD-1( )CXCR3( ) T 滤泡辅助细胞有助于在流感疫苗接种后产生高亲和力抗体。

• 发表时间: 2016-05-27
• 影响因子: 4.6
• 作者: Bentebibel SE;Khurana S;Schmitt N;Kurup P;Mueller C;Obermoser G;Palucka AK;Albrecht RA;Garcia-Sastre A;Golding H;Ueno H
• 通讯作者: Ueno H

Infection in Health Personnel with High and Low Levels of Exposure in a Hospital Setting during the H1N1 2009 Influenza A Pandemic.

2009 年 H1N1 甲型流感大流行期间医院环境中高水平和低水平暴露的卫生人员的感染。

• 发表时间: 2016
• 影响因子: 3.7
• 作者: Sandoval, Carmen;Barrera, Aldo;Ferrés, Marcela;Cerda, Jaime;Retamal, Javiera;García;Medina, Rafael A;Hirsch, Tamara
• 通讯作者: Hirsch, Tamara

Turkey versus guinea pig red blood cells: hemagglutination differences alter hemagglutination inhibition responses against influenza A/H1N1.

火鸡与豚鼠红细胞：血凝差异改变针对甲型/H1N1流感的血凝抑制反应。

• 发表时间: 2014-05
• 影响因子: 2.2
• 作者: Ovsyannikova, Inna G;White, Sarah J;Albrecht, Randy A;García;Poland, Gregory A
• 通讯作者: Poland, Gregory A