BLR&D Research Career Scientist Award
BLR
基本信息
- 批准号:10265409
- 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:2019
- 资助国家:美国
- 起止时间:2019-04-01 至 2024-03-31
- 项目状态:已结题
- 来源:
- 关键词:AIDS preventionAdmission activityAffectAmino AcidsAnti-Retroviral AgentsAntibodiesAntigen-Presenting CellsAntigensAntiviral AgentsApplications GrantsAppointmentAwardBindingBiological AssayBlocking AntibodiesBook ChaptersCD4 Positive T LymphocytesCaringCategoriesCellsCellular AssayCleaved cellClinical ImmunologyCoculture TechniquesCollaborationsCommunicable DiseasesContractsDataDevelopmentDiseaseEndoplasmic ReticulumEpitopesExploratory/Developmental Grant for Diagnostic Cancer ImagingFluorescence MicroscopyFoundationsFundingGlycoproteinsGoalsGrantHIVHIV InfectionsHIV vaccineHealthHealthcare SystemsHigh School StudentIACUCImageImmuneImmune responseImmunityImmunologyIndividualInfectionInterleukin-2InvestigationIsraelKnowledgeLaboratoriesLaboratory ResearchLectinLipid BilayersMacaca mulattaMass Spectrum AnalysisMeasuresMediatingMedical centerMedicineMentorsMentorshipMolecular VirologyMutationNational Institute of Allergy and Infectious DiseaseNatureNew YorkOligosaccharidesPaperPathogenesisPathogenicityPeptide Signal SequencesPhasePhase III Clinical TrialsPolysaccharidesPost-Translational Protein ProcessingPostdoctoral FellowPredispositionProcessPropertyProviderPublicationsPublishingRecoveryReportingResearchResearch Peer ReviewResearch TrainingRiskRoleScienceScientistSiteSpecialistStreamStructureStudy SectionT-Cell ActivationT-Cell ReceptorT-LymphocyteTherapeuticTimeTrainingTrustUnited States National Institutes of HealthV3 LoopVaccinationVaccine ResearchVaccinesVeteransViral AntigensVirusVirus DiseasesWestern BlottingWorkYangcareercostcross reactivitydesigneditorialenv Gene Productsfallsfrontierglycosylationgraduate studenthumanized mouseimmunogenicinterestmedical schoolsmonocytemonomermouse modelneutralizing antibodynovelpathogenpreventprofessorprogramsprophylacticresponsesimian human immunodeficiency virusstandard of caretechnique developmenttoolundergraduate studentvaccine trialvaccine-induced immunityviral transmissionvirus developmentvirus envelope
项目摘要
This application is to request a renewal of the BLR&D Research Career Scientist (RCS) award for Dr.
Catarina Hioe. Dr. Hioe is a Research Health Specialist (GS13 Step 8) at the James J. Peters VA Medical
Center (JJP VAMC), Bronx, NY, and a tenured Professor of Medicine at the Icahn School of Medicine at Mount
Sinai. She joined the VA via the Merit Review Entry Program in 1998 and established her research laboratory
initially at the VA New York Harbor Healthcare System–Manhattan, moving in 2015 to the JJP VAMC. She
received an RCS award (10/1/12-9/30/17) and a one-year Cost Extension through 9/30/18, in part for recovery
from Superstorm Sandy (10/29/12). Despite the setback from that storm, her lab continues to excel, as
evidenced by an array of accomplishments in each of the key measures that are highlighted in this application.
Over the past 20 years, Dr. Hioe has built a VA research program to study HIV immunology and
pathogenesis. This program is also supported by a robust non-VA research program. The Hioe lab is
investigating the immunogenic and immunopathogenic properties of the HIV envelope (Env), a glycoprotein
that may be targeted by host responses to reduce virus transmissibility and infectivity. In particular, Dr. Hioe's
studies have focused on harnessing the antiviral potential of anti-HIV Env antibodies beyond their
conventionally measured virus-neutralizing activity. The anti-Env antibodies of interest do not fall into the
broadly and potently neutralizing category but, instead, target immunogenic conserved sites and can be
generated by the vast majority of individuals. Specifically, these antibodies target the variable loops 1, 2, and 3
(V1V2 and V3), which form the apex of an HIV Env spike. Although these loops have variable amino acids,
they maintain conserved structures that are recognized by cross-reactive antibodies able to bind HIV Env of
diverse isolates from multiple subtypes. Importantly, V1V2 antibodies have been identified as an immune
correlate of reduced risk of HIV acquisition in the Thai RV144 HIV vaccine trial, the only phase III clinical trial to
show vaccine-induced protection (albeit short-lived and with a modest efficacy of 31.2%). Antibodies to the V3
loop also correlated with lower rates of HIV acquisition in a subset of RV144 vaccine recipients.
As a result of their research into how anti-V1V2 and -V3 antibodies confer this protection, the Hioe lab has
demonstrated the following major findings: 1) Although V1V2 and V3 antibodies display no or poor activity in
standard neutralization assays, their neutralizing activity can be enhanced by prolonging the time allowed for
virus-antibody interaction; this is indicative of the highly dynamic nature of HIV Env, which affects V1V2 and V3
accessibility to antibodies. 2) V1V2 and V3 exposure is also regulated by N-glycans that shroud the virus Env;
glycan composition is dictated in part by Env signal sequence. Hence, virus susceptibility to V1V2 and V3
antibodies is modulated by signal sequence changes. 3) V1V2 and V3 antibodies block the HIV Env
costimulatory activity that enhances CD4 T cell activation and renders the cells more susceptible to infection.
This costimulatory activity is dependent on T-cell receptor engagement and antigen-presenting cells (APCs),
does not require infectious virus, and can be triggered by monomeric Env with accessible V1V2 and V3,
allowing effective blockade by antibodies against these regions. 4) Finally, passive transfer of V1V2 and V3
antibodies results in control of HIV infection in the humanized mouse model, similar to that seen in rhesus
macaques challenged with a chimeric SHIV virus. Dr. Hioe has published 32 peer-reviewed research articles
over the past 10 years to report these and other, related studies. She has mentored >30 trainees and
participated in numerous committees within and outside the VA. She also has been awarded a number of
grants: In 2017 and 2018, she received an NIH R21 award to study the role of signal sequence in regulating
HIV Env expression and glycosylation, an NIH R01 grant to assess antiviral mechanisms of non-neutralizing
antibodies, and a VA Merit Review award to evaluate HIV interaction with antibodies and APCs.
此申请是为了申请续签BLR&D研究职业科学家(RCS)奖。
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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Catarina E Hioe其他文献
Catarina E Hioe的其他文献
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{{ truncateString('Catarina E Hioe', 18)}}的其他基金
COVID-19: Significance of Fc properties and functions in antibody responses against SARS-CoV-2
COVID-19:Fc 特性和功能在针对 SARS-CoV-2 的抗体反应中的重要性
- 批准号:
10609822 - 财政年份:2022
- 资助金额:
-- - 项目类别:
COVID-19: Significance of Fc properties and functions in antibody responses against SARS-CoV-2
COVID-19:Fc 特性和功能在针对 SARS-CoV-2 的抗体反应中的重要性
- 批准号:
10365140 - 财政年份:2022
- 资助金额:
-- - 项目类别:
Biologic consequences of HIV-1 interaction with bacteria
HIV-1 与细菌相互作用的生物学后果
- 批准号:
10263148 - 财政年份:2020
- 资助金额:
-- - 项目类别:
Harnessing Abs specific for immunogenic and conserved Env epitopes to protect against HIV
利用免疫原性和保守的 Env 表位特异性抗体来预防 HIV
- 批准号:
10153678 - 财政年份:2018
- 资助金额:
-- - 项目类别: