COVID19: Anti-SARS-CoV-2 Antibodies and Infection Severity

COVID19:抗 SARS-CoV-2 抗体和感染严重程度

基本信息

项目摘要

The new Covid-19 virus is deadly for 0.2% to 4% of people infected, with older men the most severely afflicted with this scourge, being mortal to ~15% of those infected over 80 years, making the US Veteran population especially vulnerable. It is critically important to understand the mechanisms of this lethal pathophysiology in order to design interventions that will save lives. MERS, SARS-CoV, and now the new human Covid-19 mean that three coronaviruses have threatened to become horrific public health problems for the entire world; this last and most recent one, Covid-19, has succeeded. Some of the antibodies formed against this virus appear to accentuate the clinical severity of disease, possibly making the specific details of the immune response responsible for the demise of many infected patients. We have had more than two decades of experience as VA Merit supported investigators exploring the antigenic structure of the lupus autoantigens, leading us to the theory that Epstein-Barr virus causes lupus, which is a hypothesis now supported by convincing circumstantial evidence. We propose to apply our experience to exploring the details of the fine antigenic specificity of the anti-Covid-19 antibody response in order to understand what specific antibodies are dangerous. We propose to explore two hypotheses: Hypothesis 1. Specific and detailed knowledge of antibody immune responses to Covid-19 will be useful for elucidating pathogenic mechanisms, predicting disease severity, designing vaccines, selecting therapeutic plasmas, making patient care decisions, informing population epidemiology, determining infection dynamics, and choosing individual behaviors in the face of the Covid-19 pandemic. Hypothesis 2. Anti-Covid-19 antibody fine antigenic specificity will correlate with clinical manifestations and infection severity. We propose two aims: Aim 1. Develop and apply assays to dissect the antigenic fine specificity of antibodies forming against shared and sub-strain specific Covid-19 antigens in the natural human Covid-19 infection. Aim 2. Isolate and purify anti-Covid-19 antibodies against the major epitopes and any specific antibodies that are associated with severe pulmonary disease. We will use Western blotting, solid phase assays (ELISAs), phage display libraries expressing 30-mer amino acid peptides, and synthesized overlapping fmoc peptides to fully characterize the fine specificity antibody response to the Covid-19 virus. We will obtain plasma and serum from Veterans and others which we will evaluate for correlates with clinical outcome. We will isolate individual specificities and characterize their properties with respect to type, isotype, glycosylation, and activity. We will perform pseudotype assays on whole repertoires and individual antibody specificities in BSL2 and test for confirmation with neutralization with collaborators with BSL3 facilities. From these studies we hope to learn how to identify Veterans who are likely to have a more severe illness and provide clues for developing approaches that could succeed in ameliorating infection severity and prevent severe disease.
新的Covid-19病毒对0.2%至4%的感染者是致命的,老年男性受影响最严重 随着这一祸害,在80年内,15%的感染者会死亡,使美国退伍军人人口 尤其脆弱。了解这种致命的病理生理机制是至关重要的, 为了设计能够拯救生命的干预措施。MERS、SARS-CoV,以及现在新的人类Covid-19意味着 三种冠状病毒有可能成为全世界可怕的公共卫生问题;这 上一次也是最近一次的新冠肺炎疫情取得了成功。 针对这种病毒形成的一些抗体似乎加重了疾病的临床严重性, 使得免疫反应的具体细节对许多感染患者的死亡负责。我们 作为VA Merit支持研究人员探索抗原性的研究人员, 狼疮自身抗原的结构,导致我们的理论,EB病毒引起狼疮,这是一个 现在有令人信服的间接证据支持这一假设。我们建议将我们的经验应用于 探索抗Covid-19抗体反应的精细抗原特异性的细节,以便 了解哪些特定的抗体是危险的。我们提出两个假设: 假设1.将提供有关Covid-19抗体免疫反应的具体和详细知识, 用于阐明致病机制,预测疾病严重程度,设计疫苗, 选择治疗性等离子体,做出患者护理决策,告知人群流行病学, 确定感染动态,并在面对COVID-19时选择个人行为 流行病 假设2.抗Covid-19抗体精细抗原特异性将与临床相关 表现和感染严重程度。 我们提出两个目标: 目标1。开发和应用分析方法,以剖析针对共享的抗体形成的抗原特异性 和亚株特异性Covid-19抗原在自然人Covid-19感染中的作用。 目标2.分离和纯化针对主要表位的抗Covid-19抗体和任何特异性抗体, 与严重的肺部疾病有关 我们将使用蛋白质印迹、固相分析(ELISA)、表达30-mer氨基酸的噬菌体展示文库、 酸性肽,并合成重叠的Fmoc肽,以充分表征精细的特异性抗体 对新冠病毒的反应。我们将从退伍军人和其他人那里获得血浆和血清, 评估与临床结果的相关性。我们将隔离个人的特殊性并描述他们的特征 关于类型、同种型、糖基化和活性的性质。我们将进行假型分析, BSL 2中的完整库和单个抗体特异性,并进行中和确认试验, 与BSL 3设施合作。从这些研究中,我们希望了解如何识别可能 并为开发可能成功改善的方法提供线索 严重感染和预防严重疾病。

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

KENNETH M KAUFMAN其他文献

KENNETH M KAUFMAN的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('KENNETH M KAUFMAN', 18)}}的其他基金

COVID19: Anti-SARS-CoV-2 Antibodies and Infection Severity
COVID19:抗 SARS-CoV-2 抗体和感染严重程度
  • 批准号:
    10371080
  • 财政年份:
    2021
  • 资助金额:
    --
  • 项目类别:
DNA Binding of Human and Viral Transcription Factors is Associated with Rheumatoid Arthritis Risk Loci
人类和病毒转录因子的 DNA 结合与类风湿关节炎风险位点相关
  • 批准号:
    9562248
  • 财政年份:
    2018
  • 资助金额:
    --
  • 项目类别:
DNA Binding of Human and Viral Transcription Factors is Associated with Rheumatoid Arthritis Risk Loci
人类和病毒转录因子的 DNA 结合与类风湿关节炎风险位点相关
  • 批准号:
    10045951
  • 财政年份:
    2018
  • 资助金额:
    --
  • 项目类别:
DNA Binding of Human and Viral Transcription Factors is Associated with Rheumatoid Arthritis Risk Loci
人类和病毒转录因子的 DNA 结合与类风湿关节炎风险位点相关
  • 批准号:
    10421240
  • 财政年份:
    2018
  • 资助金额:
    --
  • 项目类别:
CORE B: NUCLEIC ACID ANALYSIS CORE
核心 B:核酸分析核心
  • 批准号:
    8359788
  • 财政年份:
    2011
  • 资助金额:
    --
  • 项目类别:
SELECT SLE CANDIDATE GENES IN AFRICAN AMERICANS
选择非裔美国人中的 SLE 候选基因
  • 批准号:
    8359792
  • 财政年份:
    2011
  • 资助金额:
    --
  • 项目类别:
SELECT SLE CANDIDATE GENES IN AFRICAN-AMERICANS
选择非裔美国人中的 SLE 候选基因
  • 批准号:
    8168260
  • 财政年份:
    2010
  • 资助金额:
    --
  • 项目类别:
OK COBRE: NUCLEIC ACID ANALYSIS CORE
OK COBRE:核酸分析核心
  • 批准号:
    7960576
  • 财政年份:
    2009
  • 资助金额:
    --
  • 项目类别:
SNP Confirmation and High Throughput Genotyping Core
SNP 确认和高通量基因分型核心
  • 批准号:
    7938655
  • 财政年份:
    2009
  • 资助金额:
    --
  • 项目类别:
Comprehensive Genotyping for Susceptibility to Metabolic Muscle Disease
代谢性肌肉疾病易感性的综合基因分型
  • 批准号:
    7539777
  • 财政年份:
    2008
  • 资助金额:
    --
  • 项目类别:

相似海外基金

Double Incorporation of Non-Canonical Amino Acids in an Animal and its Application for Precise and Independent Optical Control of Two Target Genes
动物体内非规范氨基酸的双重掺入及其在两个靶基因精确独立光学控制中的应用
  • 批准号:
    BB/Y006380/1
  • 财政年份:
    2024
  • 资助金额:
    --
  • 项目类别:
    Research Grant
Quantifying L-amino acids in Ryugu to constrain the source of L-amino acids in life on Earth
量化 Ryugu 中的 L-氨基酸以限制地球生命中 L-氨基酸的来源
  • 批准号:
    24K17112
  • 财政年份:
    2024
  • 资助金额:
    --
  • 项目类别:
    Grant-in-Aid for Early-Career Scientists
Collaborative Research: RUI: Elucidating Design Rules for non-NRPS Incorporation of Amino Acids on Polyketide Scaffolds
合作研究:RUI:阐明聚酮化合物支架上非 NRPS 氨基酸掺入的设计规则
  • 批准号:
    2300890
  • 财政年份:
    2023
  • 资助金额:
    --
  • 项目类别:
    Continuing Grant
Basic research toward therapeutic strategies for stress-induced chronic pain with non-natural amino acids
非天然氨基酸治疗应激性慢性疼痛策略的基础研究
  • 批准号:
    23K06918
  • 财政年份:
    2023
  • 资助金额:
    --
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Molecular mechanisms how arrestins that modulate localization of glucose transporters are phosphorylated in response to amino acids
调节葡萄糖转运蛋白定位的抑制蛋白如何响应氨基酸而被磷酸化的分子机制
  • 批准号:
    23K05758
  • 财政年份:
    2023
  • 资助金额:
    --
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Molecular recognition and enantioselective reaction of amino acids
氨基酸的分子识别和对映选择性反应
  • 批准号:
    23K04668
  • 财政年份:
    2023
  • 资助金额:
    --
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Design and Synthesis of Fluorescent Amino Acids: Novel Tools for Biological Imaging
荧光氨基酸的设计与合成:生物成像的新工具
  • 批准号:
    2888395
  • 财政年份:
    2023
  • 资助金额:
    --
  • 项目类别:
    Studentship
Structurally engineered N-acyl amino acids for the treatment of NASH
用于治疗 NASH 的结构工程 N-酰基氨基酸
  • 批准号:
    10761044
  • 财政年份:
    2023
  • 资助金额:
    --
  • 项目类别:
Lifestyle, branched-chain amino acids, and cardiovascular risk factors: a randomized trial
生活方式、支链氨基酸和心血管危险因素:一项随机试验
  • 批准号:
    10728925
  • 财政年份:
    2023
  • 资助金额:
    --
  • 项目类别:
Single-molecule protein sequencing by barcoding of N-terminal amino acids
通过 N 端氨基酸条形码进行单分子蛋白质测序
  • 批准号:
    10757309
  • 财政年份:
    2023
  • 资助金额:
    --
  • 项目类别:
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了