Understand B Cell Immunity Against HIV-1 gp41 MPER

了解 B 细胞针对 HIV-1 gp41 MPER 的免疫

• 批准号: 8042885
• 负责人: NEIL S GREENSPAN
• 金额: $ 45.79万
• 依托单位: IOWA STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-08-01 至 2015-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8042885
• 关键词: AIDS Vaccines; AIDS vaccine development; Animals; Antibody Formation; Antigen Targeting; Antigens; B-Cell Activation; B-Lymphocyte Subsets; B-Lymphocytes; CD4 Positive T Lymphocytes; Coupled; DNA; Elements; Engineering; Enhancing Antibodies; Epitopes; Evaluation; Goals; Gold; HIV-1; Helper-Inducer T-Lymphocyte; Immune response; Immunity; Immunization; Immunobiology; Life; Link; Measures; Membrane; Memory B-Lymphocyte; Mus; Periodicity; Proteins; Research Personnel; Stimulus; Structure of germinal center of lymph node; T-Lymphocyte; TNFSF5 gene; Testing; Vaccines; Variant; base; density; immunogenic; immunogenicity; in vivo; nanoparticle; neutralizing antibody; novel; novel strategies; novel vaccines; pathogen; research study; response; self assembly; vaccine delivery

Investigators in Project 2 will focus on evaluation of B cell immune responses against gp41-MPER antigens being delivered by different platforms. The specific aims are: Aim 1. To compare B cell responses to monovalent vs. multivalent gp41 MPER antigens. Using multivalent antigen delivery platforms developed in Aims 1 and 2, we will test our hypothesis that multivalent antigens are capable of inducing antibody responses that are superior to monovalent antigens, qualitatively and quantitatively. We will also test a second hypothesis that it is possible to preferentially elicit stronger antibody responses towards a particular epitope (e.g. 2F5 or 4E10 epitopes) by immunizing with multiple variants of the same antigen where the only conserved element amongst all the variants is the target epitope. Aim 2. To enhance B cell immune responses by co-presentation of costimulatory molecules. Our goal is to enhance antibody responses against multivalent antigens using costimulatory molecules. In this regard, we will test our hypothesis that antibody responses against antigens will be stimulated to a greater extent when costimulatory molecules are physically linked to antigens (as they would be in our delivery platforms), compared to when then are presented as free molecules. We will evaluate stimulatory effects of CDI54 and BLyS. Aim 3. To compare the ability of different gp41 immunogens to elicit TFH and GC responses in vivo. Using the gp41 MPER multimers coupled with the different delivery platforms described in Project 1 (GNP or DNA based arrays) and with the co-stimuli described in Aim 2 of this Project, our goal will be to assess the in vivo CD4+ T helper cell and B cell response after immunization. Specifically, we will challenge mice with each of the engineered gp41 vaccines, and measure the T follicular helper (TFH) cell and germinal center (GC) response after a single exposure, and the memory B cell response after single or multiple exposures These findings will be correlated with anti-gp41 antibody responses measured in Aims 1 and 2.

项目2中的研究人员将着重于评估B细胞免疫反应，以针对不同平台提供的GP41-MPer抗原。具体目的是： 目的1。比较B细胞反应与单价与多价GP41 MPer抗原的反应。使用AIM 1和2中开发的多价抗原递送平台，我们将测试假设多价抗原能够诱导优于单价抗原（定性和定量）诱导抗体反应。我们还将检验第二个假设，即有可能优先引起对特定表位（例如2f5或4e10表位）的更强抗体反应 同一抗原的变体中，所有变体中唯一保守的元素是目标表位。 目的2。通过共刺激分子的共表达增强B细胞免疫反应。我们的目标是使用共刺激分子增强针对多价抗原的抗体反应。在这方面，我们将检验我们的假设，即当伴奏分子与抗原物理相关时（就像在我们的递送平台中一样），与抗原的抗体反应将在更大程度上受到刺激。我们将评估CDI54和Blys的刺激作用。 目标3。比较不同GP41免疫原子在体内引起TFH和GC反应的能力。使用该项目1（GNP或DNA基于DNA的阵列）中描述的不同输送平台的GP41 MPER多聚体以及该项目AIM 2中描述的共刺激性，我们的目标是评估免疫后体内CD4+ T Helper细胞和B细胞响应。具体而言，我们将使用每种工程的GP41疫苗来挑战小鼠，并在一次暴露后测量T卵泡助手（TFH）细胞（TFH）细胞和生发中心反应，以及一次或多个暴露后的记忆B细胞响应 这些发现将与目标1和2中测得的抗GP41抗体反应相关。