Project 3: Defining the antibody landscape after SARS-CoV-2 infection
项目 3:定义 SARS-CoV-2 感染后的抗体格局
基本信息
- 批准号:10221910
- 负责人:
- 金额:$ 85.51万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-09-30 至 2022-08-31
- 项目状态:已结题
- 来源:
- 关键词:2019-nCoVAntibodiesAntibody ResponseAntibody titer measurementAutoimmunityBiological AssayCOVID-19COVID-19 pandemicCellsCharacteristicsClinicalComplementComplement ActivationComplement-Dependent CytotoxicityDataDiseaseEnrollmentGoalsImmune responseImmunityImmunoglobulin AImmunoglobulin Class SwitchingImmunoglobulin GImmunoglobulin MImmunoglobulinsIndividualInfectionKineticsLinear RegressionsMeasuresMediatingMethodsModelingPathogenesisPathologyPatientsPhasePlasmaPopulationPositioning AttributeProspective cohortProteinsPublic HealthRegression AnalysisResearch PersonnelResearch Project GrantsResolutionResourcesRoleSamplingSerologicalSerumSeverity of illnessSurvivorsTimeVaccinationVariantVirionVirusVirus DiseasesWorkantibody-dependent cell cytotoxicitycohortdimerexperienceinfluenzavirusmaleneutralizing antibodypandemic diseaseprospectivereceptor bindingresponsesample fixationvaccine developmentvirology
项目摘要
Research Project 3 Summary
There are insufficient data regarding the long-term humoral immune responses induced after SARS-CoV-2
infection. Our preliminary data indicate that there is variation in the magnitude and duration of antibody
responses following SARS-CoV-2 infection. While IgG and IgA antibodies against spike (S) and the receptor
binding domain of S (S-RBD) appear to remain constant over time, neutralizing antibody (nAb) titers wane and
are not detected in up to 25% of infected individuals who have detectable anti-S and anti-S-RBD antibodies.
We have also observed that during the convalescent phase of SARS-CoV-2 infection, individuals with more
severe COVID-19 (i.e., hospitalized, older, and male patients) have significantly greater serological responses
to SARS-CoV-2. The antibody responses mediating protection from re-infection are not defined, and neither
are responses that may mediate greater pathology. From studies of other viruses, it is clear that a variety of
antibody functions contribute to protection from re-infection and modulate disease severity. Both nAbs and
non-nAbs can mediate a number of different activities, which include complement activation and antibody-
dependent cellular cytotoxicity (ADCC), which may contribute to pathogenesis as well as protections from
SARS-CoV-2. The overarching goal of JH-EPICS Research Project 3 is to analyze the magnitude and duration
of the total as well as functional antibody responses after SARS-CoV-2 infection. We have developed a core
set of serological assays to be applied to a prospective, demographically diverse cohort of hospitalized patients
presenting with mild, moderate, and severe COVID-19 disease. Plasma samples have and will continue to be
collected at multiple timepoints from enrollment through one year post-enrollment. Aim 1 will systematically
evaluate antibody isotype switching and the subclasses and quality of the immunoglobulins (IgG, IgM, and IgA
[monomeric and dimeric]) that recognize the SARS-CoV-2 S and S-RBD. Aim 2 will characterize the kinetics
and duration of the neutralizing antibody response against SARS-CoV-2 and the ability of viruses to escape
from nAbs. Finally, Aim 3 will analyze the function of non-neutralizing SARS-CoV-2-specific serological
response by assessing ADCC, complement-mediated cytotoxicity, and complement fixation activity toward
SARS-CoV-2 virus particles and virus-infected cells. Using linear regression analyses and modeling of these
data in the context of clinical and demographic information, we are uniquely positioned to determine the
modifiers that drive a protective antibody response following SARS-CoV-2 infection or, eventually, vaccination.
研究项目3总结
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)
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SABRA L. KLEIN其他文献
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{{ truncateString('SABRA L. KLEIN', 18)}}的其他基金
2023 Sex Differences in Immunity Gordon Research Conference
2023 年免疫性别差异戈登研究会议
- 批准号:
10721480 - 财政年份:2023
- 资助金额:
$ 85.51万 - 项目类别:
Project 3: Defining the antibody landscape after SARS-CoV-2 infection
项目 3:定义 SARS-CoV-2 感染后的抗体格局
- 批准号:
10688368 - 财政年份:2020
- 资助金额:
$ 85.51万 - 项目类别:
Sex and Age Differences in Immunity to Influenza (SADII)
流感免疫力的性别和年龄差异 (SADII)
- 批准号:
10213168 - 财政年份:2018
- 资助金额:
$ 85.51万 - 项目类别:
Genetic and hormonal mechanisms of sex differences in immune responses and influenza vaccine efficacy in young and aged mice
年轻和老年小鼠免疫反应和流感疫苗功效性别差异的遗传和激素机制
- 批准号:
10213173 - 财政年份:2018
- 资助金额:
$ 85.51万 - 项目类别:
Sex and Age Differences in Immunity to Influenza (SADII)
流感免疫力的性别和年龄差异 (SADII)
- 批准号:
10649070 - 财政年份:2018
- 资助金额:
$ 85.51万 - 项目类别:
Sex and Age Differences in Immunity to Influenza (SADII)
流感免疫力的性别和年龄差异 (SADII)
- 批准号:
10261763 - 财政年份:2018
- 资助金额:
$ 85.51万 - 项目类别:
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