THE MUCOSAL DENDRITIC CELL-T CELL MILIEU AND SIV SPREAD
THE MUCOSAL DENDRITIC CELL-T CELL MILIEU AND SIV SPREAD
批准号:
8358075
负责人:
Melissa J Robbiani
金额:
$5.78万
依托单位国家:
美国
项目类别:
财政年份:
2011
资助国家:
美国
项目状态:
已结题
起止时间:
2011-05-01 至 2012-04-30
关键词:
AgonistAnimalsAttenuatedBloodClinicalCoculture TechniquesDendritic CellsDouble-Stranded RNAEventFundingGrantHIVHIV InfectionsHumanImmuneImmune responseIn VitroInfectionInterferon Type IIInterleukin-17Interleukin-2MacacaMacaca mulattaNational Center for Research ResourcesNatural ImmunityPlasmaPoly I-CPoly ICLCPrimatesPrincipal InvestigatorProductionResearchResearch InfrastructureResourcesSIVSignal TransductionSourceT cell responseT-LymphocyteT-Lymphocyte SubsetsTLR3 geneTNF geneTimeToll-like receptorsUnited States National Institutes of HealthViralViral Load resultVirusVirus Receptorsanalogcostenzyme linked immunospot assayin vivomutantnovelpreventrectalresponse
中文摘要
这个子项目是利用这些资源的众多研究子项目之一
英文摘要
This subproject is one of many research subprojects utilizing the resources
provided by a Center grant funded by NIH/NCRR. Primary support for the subproject
and the subproject's principal investigator may have been provided by other sources,
including other NIH sources. The Total Cost listed for the subproject likely
represents the estimated amount of Center infrastructure utilized by the subproject,
not direct funding provided by the NCRR grant to the subproject or subproject staff.
Our studies aim to dissect the earliest events in rectal HIV/SIV infection in order to understand how HIV infection is established and spreads, and explore novel immunomodulatory strategies to prevent mucosal infection. Toll-like receptor (TLR) agonists can boost innate immunity through DC activation, with TLR3 the best characterized receptor of viral dsRNA. Poly(IC) is a synthetic dsRNA analog known to activate human and macaque DCs through both TLR3-dependent and independent mechanisms, and clinical grade poly(IC) (poly(ICLC) or Hiltonol) is commercially available and being used in humans, underscoring the potential for this mode of activation to be developed as an anti-HIV strategy. We have shown in vitro that poly(IC) signaling blocks HIV infection in DCs and DC-T cell co-cultures. Thus, we hypothesized that rectal application of Hiltonol in vivo might similarly activate mucosal DCs, triggering their immunostimulatory capability and limiting SIV replication while boosting protective immune responses. We are comparing the effects of Hiltonol on rectal challenge of Indian rhesus macaques with wt and the attenuated virus ¿nef (nef deletion mutant) because we postulated that the effects of Hiltonol would be more pronounced in a setting devoid of the immune suppressive effects of nef, and where the attenuated replication of ¿nef and its protective capacity against subsequent wt challenge would be enhanced. Following Hiltonol application and challenge, we are continuing to follow the animals over time for viral and immune parameters elicited in response to Hiltonol/SIV: plasma viral load, changes to blood DC and T cell subset numbers and activation, CK/CC levels, Ab production, and T cell responses (ELISPOT for IFN gamma and ICS for IFN gamma, TNF gamma, IL-2, and IL-17 secretion).
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会议论文
A novel vaginal ring to prevent HIV and HSV-2 infection, as well as pregnancy
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批准号:8450072
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项目类别:
-
资助金额:$19.42万
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财政年份:2012
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负责人:Melissa J Robbiani
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依托单位:
A novel vaginal ring to prevent HIV and HSV-2 infection, as well as pregnancy
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批准号:8264696
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项目类别:
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资助金额:$23.05万
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财政年份:2012
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负责人:Melissa J Robbiani
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依托单位:
HIV ENVELOPE SPECIFIC DARPIN-BASED MICROBICIDE
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批准号:8358133
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项目类别:
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资助金额:$5.78万
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财政年份:2011
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负责人:Melissa J Robbiani
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依托单位:
ZCM:A NOVEL BROAD-SPECTRUM MICROBICIDE FOR SEXUALLY TRANSMITTED INFECTIONS
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批准号:8358089
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项目类别:
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资助金额:$5.78万
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财政年份:2011
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负责人:Melissa J Robbiani
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依托单位:
IMPACT OF ART ON DC & TREG RESPONSES
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批准号:8358115
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项目类别:
-
资助金额:$5.78万
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财政年份:2011
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负责人:Melissa J Robbiani
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依托单位:
BLOCKING VIRUS SPREAD BY DCS WITH CARRAGEENAN-BASED COMPOUNDS
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批准号:8358043
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项目类别:
-
资助金额:$5.78万
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财政年份:2011
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负责人:Melissa J Robbiani
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依托单位:
DENDRITIC CELL ACTIVATION BY ISS ODN FOR SIV IMMUNITY
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批准号:8358061
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项目类别:
-
资助金额:$5.78万
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财政年份:2011
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负责人:Melissa J Robbiani
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依托单位:
HIV ENVELOPE SPECIFIC DARPIN-BASED MICROBICIDE
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批准号:8173046
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项目类别:
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资助金额:$6.18万
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财政年份:2010
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负责人:Melissa J Robbiani
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依托单位:
ZCM:A NOVEL BROAD-SPECTRUM MICROBICIDE FOR SEXUALLY TRANSMITTED INFECTIONS
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批准号:8172989
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项目类别:
-
资助金额:$6.18万
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财政年份:2010
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负责人:Melissa J Robbiani
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依托单位:
THE MUCOSAL DENDRITIC CELL-T CELL MILIEU AND SIV SPREAD
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批准号:8172970
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项目类别:
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资助金额:$6.18万
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财政年份:2010
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负责人:Melissa J Robbiani
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依托单位:
DENDRITIC CELL ACTIVATION BY ISS ODN FOR SIV IMMUNITY
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批准号:8172955
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项目类别:
-
资助金额:$6.18万
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财政年份:2010
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负责人:Melissa J Robbiani
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依托单位:
BLOCKING VIRUS SPREAD BY DCS WITH CARRAGEENAN-BASED COMPOUNDS
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批准号:8172934
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项目类别:
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资助金额:$6.18万
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财政年份:2010
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负责人:Melissa J Robbiani
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依托单位:
IMPACT OF ART ON DC & TREG RESPONSES
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批准号:8173027
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项目类别:
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资助金额:$6.18万
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财政年份:2010
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负责人:Melissa J Robbiani
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依托单位:
BLOCKING VIRUS SPREAD BY DCS WITH CARRAGEENAN-BASED COMPOUNDS
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批准号:7958592
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项目类别:
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资助金额:$5.81万
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财政年份:2009
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负责人:Melissa J Robbiani
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依托单位:
HIV-envelope-specific DARPin-based microbicide strategies
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批准号:8313900
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项目类别:
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资助金额:$69.44万
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财政年份:2009
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负责人:Melissa J Robbiani
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依托单位:
IMPACT OF ART ON DC & TREG RESPONSES
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批准号:7958720
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项目类别:
-
资助金额:$5.81万
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财政年份:2009
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负责人:Melissa J Robbiani
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依托单位:
HIV-envelope-specific DARPin-based microbicide strategies
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批准号:7737766
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项目类别:
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资助金额:$48.84万
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财政年份:2009
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负责人:Melissa J Robbiani
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依托单位:
ZCM:A NOVEL BROAD-SPECTRUM MICROBICIDE FOR SEXUALLY TRANSMITTED INFECTIONS
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批准号:7958669
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项目类别:
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资助金额:$3.63万
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财政年份:2009
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负责人:Melissa J Robbiani
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依托单位:
HIV-envelope-specific DARPin-based microbicide strategies
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批准号:8134855
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项目类别:
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资助金额:$74.53万
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财政年份:2009
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负责人:Melissa J Robbiani
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依托单位:
DENDRITIC CELL ACTIVATION BY ISS ODN FOR SIV IMMUNITY
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批准号:7958618
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项目类别:
-
资助金额:$5.81万
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财政年份:2009
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负责人:Melissa J Robbiani
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依托单位:
海外基金