Characterization of T & B cell responses correlated with broad neutralizing Abs
Characterization of T & B cell responses correlated with broad neutralizing Abs
批准号:
7663383
负责人:
Spyros A Kalams
金额:
$53.16万
依托单位国家:
美国
项目类别:
财政年份:
2009
资助国家:
美国
项目状态:
已结题
起止时间:
2009-07-16 至 2014-06-30
关键词:
Acquired Immunodeficiency SyndromeAnti-Retroviral AgentsAntibodiesAntibody FormationAutologousB-Cell ActivationB-LymphocytesBiological AssayCD4 Positive T LymphocytesCD8B1 geneCell physiologyChronicDataDevelopmentDisease ProgressionEarly identificationFaceGenerationsGoalsHIVHIV InfectionsHIV vaccineHelper-Inducer T-LymphocyteHumanImmune responseImmunityIn VitroIndividualInfectionInstructionMaintenanceMeasuresOutcomeReagentRoleSorting - Cell MovementSystemT-LymphocyteTestingTimeVaccinatedVaccinationVaccinesViralViral ProteinsViremiaVirusadvanced diseaseassay developmentcohortdesignneutralizing antibodynew technologyprogramsresponsevaccine candidatevaccine development
中文摘要
一种有效的艾滋病毒疫苗需要引起有效的体液和细胞免疫反应
英文摘要
An effective HIV vaccine will need to elicit potent humoral and cellular immune responses for true
sterilizing immunity. HIV-specific CD4 + T cell responses, particularly proliferative responses, are a potent
correlate of control of viremia, but relatively uncommon and of low magnitude in HIV infected individuals.
Autologous neutralizing antibodies in HIV infected subjects are typically of low titer, and lack sufficient
breadth to neutralize heterologous viruses. Our current HIV vaccine candidates currently under testing in
humans are able to elicit CD8+ cellular immune responses, and may well provide partial protection against
infection, but are unlikely to generate neutralizing antibodies. This HIVRAD program project will identify viral
sequences that elicit broadly neutralizing antibodies in subjects with varying degrees of control of viremia.
This particular project (project 2) will take advantage of our access to a large cohort of subjects with early
and chronic HIV infection, and which contains several individuals with control of viremia in the absence of
anti-retroviral therapy. From years of expertise studying cellular immune responses, and from our preliminary
data, we know several of these individuals have intact virus-specific CD4+ T cell responses. Our goalwith
this project is to identify interactions between CD4+ T cells and B cells that predict the ability of HIV-infected
individuals to generate broadly neutralizing antibodies. We have also designed new technology that allows
us to sort B cells specific for HIV envelope, which we will use to isolate B cell clones from subjects with
broadly neutralizing antibody activity. The outcome of this project will be a comprehensive picture of helper
function required to maintain B cell responses, assays to assess CD4-B cell function in chronically infected
and vaccinated individuals, and new antibody reagents that will be used to further characterize HIV
neutralizing activity.
RELEVANCE (See instructions):
Understanding the factors that allow the generation of broadly neutralizing antibodies is critical to vaccine
development. In this project we will explore the hypothesis that intact interactions between T cells and B cells
is critical to the development and maintenance of broadly neutralizing antibodies in HIV-infected individuals.
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依托单位:
TCR GENE USAGE AND QUANTITATION OF HIV SPECIFIC CTL
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财政年份:1997
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TCR GENE USAGE AND QUANTITATION OF HIV SPECIFIC CTL
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海外基金