COVID-19: Elucidating monoclonal and polyclonal seroantibody responses to the COVID-19 viral envelope
COVID-19:阐明对 COVID-19 病毒包膜的单克隆和多克隆血清抗体反应
基本信息
- 批准号:10513290
- 负责人:
- 金额:--
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-10-01 至 2024-09-30
- 项目状态:已结题
- 来源:
- 关键词:2019-nCoVAcuteAffinity ChromatographyAmericanAnimalsAntibodiesAntibody ResponseAntigensAwardB-LymphocytesBindingBinding SitesBiochemicalBiological AssayCOVID-19COVID-19 pandemicCOVID-19 patientCOVID-19 preventionCategoriesCellsCessation of lifeCharacteristicsChargeCodon NucleotidesCoronavirusDiseaseDoctor of PhilosophyElectrophoresisEnrollmentEpitope MappingEpitopesFamilyFractionationGoalsHIVHandHealthHealthcare SystemsHumanImmunityImmunoglobulin AImmunoglobulin GIndividualInfectionInpatientsIsoelectric PointKnowledgeLibrariesMapsMarylandMass Spectrum AnalysisMedicalMembrane GlycoproteinsMemory B-LymphocyteMethodsMonoclonal AntibodiesNucleoproteinsOutpatientsPatientsPersonsPhasePlasmaPlasmablastPlasmidsPrevention strategyProductionProteinsProtocols documentationResearchRunningSARS-CoV-2 antibodySARS-CoV-2 infectionSARS-CoV-2 spike proteinSamplingSystemTechniquesTestingUnited StatesUniversitiesVaccinesVeteransViralVirusX-Ray Crystallographybiosafety level 3 facilityconvalescent plasmaenv Gene Productsexperienceexperimental studyinterestmultiple myeloma M Proteinneutralizing antibodynovel therapeuticsnovel vaccinespandemic diseaseparticipant enrollmentpolyclonal antibodyprogramsreceptor bindingresponsetreatment strategy
项目摘要
Background/Rationale: As the Coronavirus Disease 2019 (COVID-19) epidemic expands across the United
States and the world, there are no proven therapies and little information is known regarding on immunity to
this virus. At this stage of the pandemic, all prevention and treatment strategies that show promise must be
explored. This proposal will focus on the polyclonal and monoclonal antibody responses to the severe acute
respiratory syndrome coronavirus-2 (SARS-CoV-2) envelope.
Objectives: The overarching goal of this program is to obtain a comprehensive understanding of the
polyclonal and monoclonal response to the SARS-CoV-2 envelope E, M, and S proteins. The specific aims of
this proposal are: 1) Deconvolute the polyclonal antibody response against the viral envelope of SARS-CoV-2;
2) Isolate neutralizing and non-neutralizing monoclonal antibodies against various epitopes of spike protein (S),
envelope protein (E), and membrane glycoprotein (M) of SARS-CoV-2; and 3) Map the corresponding
epitope(s) of the monoclonal antibodies.
Methods: We will obtain paired, acute and convalescent, samples from 60 inpatients and outpatients with
COVID-19 (30 have already been enrolled from the VA Maryland Health Care System and the University of
Maryland Medical System). We will screen samples by binding, live and pseudovirus neutralization. In this
proposal, we also will have access to BSL3 facilities on this campus that run neutralization assay with live virus
by one of the world experts in coronaviruses (Matt Frieman, PhD). Donors will be ranked on the basis of both
neutralization potency and breadth, and binding. The top three donors in each of the inpatient and outpatient
groups will be chosen for further study (top anti-RBD neutralization and breath, top anti- receptor binding domain
(RBD)-depleted plasma neutralization and breath, and top spike binding titers with non-neutralizing plasma).
In these six individuals, the anti-envelope antibody will be affinity purified; and fractionated using free-
flow-electrophoresis. This technique can separate antibodies based on charge, which will lead to separation
based on targeted epitopes as well. Individual fractions will be tested by binding and neutralization; and
characteristic biochemical and functional signatures of antibodies targeting each epitope will be ascertained.
Fractions of interest (different for each donor depending if neutralization or binding is targeted) will be sent for
mass spectrometry. B cell libraries will also be made from the convalescent IgG and IgA memory B cell pools;
and they will be interrogated using three complementary techniques including - acute phase plasmablast
repertoire analysis, subtraction analysis, and antigen baiting to identify potential antibodies.
Finally, mass spectrometry will be used to rank antibody candidates. 40 monoclonal antibodies (mAbs)
will be made and again be screened by neutralization potency, breadth, and isoelectric point, with top neutralizing
and binding antibodies (matching the respective profiles of the fractions that were targeted) to be moved forward
for fine epitope analysis by X-ray crystallography.
Impact: If successful, this project will yield a substantial understanding of neutralizing/non-neutralizing
antibodies and epitopes in COVID-19 disease, providing mAbs that can be moved into animal/human testing.
This research has direct relevance to the health of Veterans as any monoclonal antibodies isolated can
potentially be used for treatment and/or prevention of COVID-19.
背景/理由:随着2019年冠状病毒病(COVID-19)疫情在美国蔓延
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 }}
Mohammad Mohseni Sajadi其他文献
Mohammad Mohseni Sajadi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('Mohammad Mohseni Sajadi', 18)}}的其他基金
Engineering of pan-neutralizing anti-HIV envelope antibodies
全中和抗 HIV 包膜抗体的工程
- 批准号:
10304133 - 财政年份:2019
- 资助金额:
-- - 项目类别:
Engineering of pan-neutralizing anti-HIV envelope antibodies
全中和抗 HIV 包膜抗体的工程
- 批准号:
9927080 - 财政年份:2019
- 资助金额:
-- - 项目类别:
Engineering of pan-neutralizing anti-HIV envelope antibodies
全中和抗 HIV 包膜抗体的工程
- 批准号:
10524019 - 财政年份:2019
- 资助金额:
-- - 项目类别:
Engineering of pan-neutralizing anti-HIV envelope antibodies
全中和抗 HIV 包膜抗体的工程
- 批准号:
10064993 - 财政年份:2019
- 资助金额:
-- - 项目类别:
HIV-1 acidic epitope discovery from broadly neutralizing seroantibodies
从广泛中和血清抗体中发现 HIV-1 酸性表位
- 批准号:
9182870 - 财政年份:2014
- 资助金额:
-- - 项目类别:
Discovery of acidic epitopes for HIV-1 broadly neutralizing seroantibodies
发现 HIV-1 广泛中和血清抗体的酸性表位
- 批准号:
9788183 - 财政年份:2014
- 资助金额:
-- - 项目类别:
HIV-1 acidic epitope discovery from broadly neutralizing seroantibodies
从广泛中和血清抗体中发现 HIV-1 酸性表位
- 批准号:
8968228 - 财政年份:2014
- 资助金额:
-- - 项目类别:
相似海外基金
Acute senescence: a novel host defence counteracting typhoidal Salmonella
急性衰老:对抗伤寒沙门氏菌的新型宿主防御
- 批准号:
MR/X02329X/1 - 财政年份:2024
- 资助金额:
-- - 项目类别:
Fellowship
Transcriptional assessment of haematopoietic differentiation to risk-stratify acute lymphoblastic leukaemia
造血分化的转录评估对急性淋巴细胞白血病的风险分层
- 批准号:
MR/Y009568/1 - 财政年份:2024
- 资助金额:
-- - 项目类别:
Fellowship
Combining two unique AI platforms for the discovery of novel genetic therapeutic targets & preclinical validation of synthetic biomolecules to treat Acute myeloid leukaemia (AML).
结合两个独特的人工智能平台来发现新的基因治疗靶点
- 批准号:
10090332 - 财政年份:2024
- 资助金额:
-- - 项目类别:
Collaborative R&D
Cellular Neuroinflammation in Acute Brain Injury
急性脑损伤中的细胞神经炎症
- 批准号:
MR/X021882/1 - 财政年份:2024
- 资助金额:
-- - 项目类别:
Research Grant
KAT2A PROTACs targetting the differentiation of blasts and leukemic stem cells for the treatment of Acute Myeloid Leukaemia
KAT2A PROTAC 靶向原始细胞和白血病干细胞的分化,用于治疗急性髓系白血病
- 批准号:
MR/X029557/1 - 财政年份:2024
- 资助金额:
-- - 项目类别:
Research Grant
Combining Mechanistic Modelling with Machine Learning for Diagnosis of Acute Respiratory Distress Syndrome
机械建模与机器学习相结合诊断急性呼吸窘迫综合征
- 批准号:
EP/Y003527/1 - 财政年份:2024
- 资助金额:
-- - 项目类别:
Research Grant
FITEAML: Functional Interrogation of Transposable Elements in Acute Myeloid Leukaemia
FITEAML:急性髓系白血病转座元件的功能研究
- 批准号:
EP/Y030338/1 - 财政年份:2024
- 资助金额:
-- - 项目类别:
Research Grant
STTR Phase I: Non-invasive focused ultrasound treatment to modulate the immune system for acute and chronic kidney rejection
STTR 第一期:非侵入性聚焦超声治疗调节免疫系统以治疗急性和慢性肾排斥
- 批准号:
2312694 - 财政年份:2024
- 资助金额:
-- - 项目类别:
Standard Grant
ロボット支援肝切除術は真に低侵襲なのか?acute phaseに着目して
机器人辅助肝切除术真的是微创吗?
- 批准号:
24K19395 - 财政年份:2024
- 资助金额:
-- - 项目类别:
Grant-in-Aid for Early-Career Scientists
Collaborative Research: Changes and Impact of Right Ventricle Viscoelasticity Under Acute Stress and Chronic Pulmonary Hypertension
合作研究:急性应激和慢性肺动脉高压下右心室粘弹性的变化和影响
- 批准号:
2244994 - 财政年份:2023
- 资助金额:
-- - 项目类别:
Standard Grant














{{item.name}}会员




