SARS-CoV-2 Vaccine Responses in children with genetic or acquired B cell deficiencies
患有遗传性或后天性 B 细胞缺陷的儿童对 SARS-CoV-2 疫苗的反应
基本信息
- 批准号:10502936
- 负责人:
- 金额:$ 62.19万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-06-02 至 2026-05-31
- 项目状态:未结题
- 来源:
- 关键词:2019-nCoV5 year oldAdolescenceAdultAffectAffinityAgeAntigensB-LymphocytesCD8-Positive T-LymphocytesCD8B1 geneCOVID-19COVID-19 disparityCOVID-19 vaccinationCOVID-19 vaccineChildChildhoodCytokeratin-8 Staining MethodDefectDiseaseExhibitsFutureGeneticGoalsGrowthImmuneImmune responseImmune systemImmunityImmunocompetentImmunoglobulin AImmunoglobulin GImmunologicsIn VitroIncidenceInfectionInterferonsKnowledgeLearningLifeLongitudinal cohortMissionMolecularMorbidity - disease rateMucous MembraneMyelogenousParticipantPathologicPathologyPersonsPhenotypePhysiologicalPopulationProductionPublic HealthRNA vaccinationRNA vaccineResearchSARS-CoV-2 B.1.617.2SARS-CoV-2 infectionSARS-CoV-2 spike proteinSerumSeveritiesT cell differentiationT cell responseTestingUnited States National Institutes of HealthVaccinatedVaccinationVaccine Clinical TrialVaccinesVirusWorkadaptive immune responseage groupbasecohortcytokinehumoral immunity deficiencyinsightmortalitymultiple sclerosis patientneutralizing antibodyprospectivereceptor bindingresponsestemtranscriptomicstransmission processvaccination strategyvaccine efficacyvaccine response
项目摘要
PROJECT SUMMARY
Emergence of the highly transmissible SARS-CoV-2 B.1.617.2 (Delta) variant and return to in-person learning
is rapidly increasing the COVID-19 disease incidence and transmission rate in children. Therefore, it is critical
to protect younger children. Toward this goal, ongoing COVID-19 vaccine clinical trials aim to reach those as
young as 6 months old. Because pediatric trials involve fewer participants and children have a lower rate of
symptomatic infection, pediatric vaccine efficacy will be initially based on in vitro immunological parameters—
virus neutralization and antibodies to the receptor-binding domain (RBD) or S1 fragment of the SARS-CoV-2
spike protein. However, whether these same metrics reflect an effective vaccine response in a developing
immune system (<5 years old) remains to be determined. Immune responses to vaccines are influenced by
age-associated physiological changes, particularly in the first 5 years of life when changes occur in B and T
cell differentiation and effector functions, affinity maturation of B cell responses, and myeloid subpopulations
and their cytokine production. Additionally, in very young children mucosal IgA rapidly reach adult levels, while
serum IgA only reaches adult levels in adolescence. This difference may account for the disparate COVID-19
disease incidence, transmission, and severity in children. How evolving changes in pediatric mucosal and
systemic immune ontogeny affect SARS-CoV-2 infection- and mRNA vaccination-elicited immune responses
are incompletely understood. The overall objective here is to define mucosal and systemic SARS-CoV-2
infection- and mRNA vaccine- elicited molecular and immune cellular responses in healthy pediatric maturing
immune systems and in pathological B cell states (inborn or acquired).
In a Pfizer-vaccinated adult cohort, compared to healthy adults, we have found that B cell depleted adult
multiple sclerosis patients exhibited a significantly increased RBD-specific CD8 T cell response, despite
negligible production of anti-RBD IgG. Interestingly, in children homeostatic and induced IgA levels are
minimally affected by B cell depleting therapies. Our central hypothesis is that mRNA vaccination within the
pediatric population augments mucosal (IFN and IgA) and CD8 T cellular immune parameters in the youngest
children (<5yo) relative to older children (>5yo). We predict that such immune profile will i) correlate with
vaccine- and infection-elicited responses, supporting their limited infection pathology (Aim 1); and ii) become
enhanced in those children with B cell deficiencies (Aim 2). To test this hypothesis and its predictions, we will i)
establish a prospective longitudinal cohort of SARS-CoV-2 infected/vaccinated healthy and B cell deficient
children across age groups; and ii) apply transcriptomic, immune phenotypic, and antigen-specific humoral and
cellular studies to compare SARS-CoV-2 vaccine- and infection-elicited molecular and cellular signatures in
healthy children and those with inborn and acquired B cell defects. Resulting insights will define
metrics
of
infection/vaccine immunity, constituting an initial step toward establishing correlates of protection in
immunocompetent/B
deficient
children.
项目总结
项目成果
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{{ truncateString('WEN-YUAN E HSIEH', 18)}}的其他基金
Spatial Mapping of Proteomic and Transcriptional Signatures in Kidney Disease
肾脏疾病蛋白质组和转录特征的空间图谱
- 批准号:
10701891 - 财政年份:2022
- 资助金额:
$ 62.19万 - 项目类别:
SARS-CoV-2 Vaccine Responses in children with genetic or acquired B cell deficiencies
患有遗传性或后天性 B 细胞缺陷的儿童对 SARS-CoV-2 疫苗的反应
- 批准号:
10633304 - 财政年份:2022
- 资助金额:
$ 62.19万 - 项目类别:
Immune Dysregulation in Pediatric SLE Pathogenesis
儿童 SLE 发病机制中的免疫失调
- 批准号:
9223553 - 财政年份:2017
- 资助金额:
$ 62.19万 - 项目类别:
Immune Dysregulation in Pediatric SLE Pathogenesis
儿童 SLE 发病机制中的免疫失调
- 批准号:
10155413 - 财政年份:2017
- 资助金额:
$ 62.19万 - 项目类别:
Immune Dysregulation in Pediatric SLE Pathogenesis
儿童 SLE 发病机制中的免疫失调
- 批准号:
9902184 - 财政年份:2017
- 资助金额:
$ 62.19万 - 项目类别:
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