Primate Studies
灵长类动物研究
基本信息
- 批准号:8720871
- 负责人:
- 金额:$ 22.05万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2011
- 资助国家:美国
- 起止时间:2011-04-01 至 2013-12-31
- 项目状态:已结题
- 来源:
- 关键词:AIDS VaccinesAddressAdjuvantAlabamaAnimalsAntibodiesAntigensBloodCCL25 geneCCL27 geneCellsCellular ImmunityDNA VaccinesDevelopmentGaggingHIVHeadHomingHumoral ImmunitiesImmuneImmune responseImmunizationIndividualIntramuscularLymph Node TissueMacacaMacaca mulattaMeasuresMediatingModelingMonkeysMucosal Immune ResponsesMucosal ImmunityMucous MembranePennsylvaniaPlasmidsPrimatesResearchResearch PersonnelRouteSIVSamplingTestingUniversitiesVaccinationVaccinesanimal efficacycell mediated immune responsechemokineenv Genesnovelnovel strategiesplasmid DNArectalresearch studytraffickingvaccine evaluation
项目摘要
The development of an effective AIDS vaccine remains one of the highest priorities in HIV-research.
Because increasing evidence suggests that an effective vaccine will require both humoral and cellular
immunity, this HIV-RAD project proposes to induce and measure both cellular and humoral immunity using
plasmid DMAconstructs expressing SIV gag,-pol-env genes plus novel chemokine DNA plasmids to address
mucosal cellular and humoral immunity. This proposal describes a new approach to inducing systemic and
mucosal immunity. The overall objective of project #3 is to evaluate the potential of intramuscular (IM)
delivery of chemokines to enhance mucosal immunity in the SIVmac model. The hypothesis to be tested is
that chemokine-induced redirected trafficking of mucosal-homing immune cells to the systemic compartment
leads to cellular and humoral mucosal immune responses without mucosal immunization.
Mucosal-expressed chemokines CTACK, MECK, TECK will be tested for their individual potential to
enhance the mucosal immune response of a systemically delivered SIV DNA vaccine. The vaccination
approach will be IM co-immunization of macaques with an optimized SIVgag/pol/env plus each plasmid form
of the mucosal-expressed chemokines. The specific aims are:
1 A. To measure antigen specific cell mediated immune responses systemically in blood as well as in the
mucosa following intramuscular plasmid co-immunization of rhesus macaques with 3 individual chemokines
plus pSIVgag/pol/env. This aim is expanded to test 5 monkeys per group compared to 3 per group in the
previous submission.
1B. To measure antigen specific antibody mediated immune responses systemically in blood and lymph
node tissues as well as in the mucosa following IM co-immunization of rhesus macaques with individual
chemokines plus pSIVgag/pol/env. Samples from animals in 1Awill also be provided to the University of
Alabama Birmingham (DAB) group headed by Dr. Jiri Mestecky.
2. To carry out animal efficacy studies using the SIVmac-rhesus model to evaluate a) 1 selected chemokine
adjuvant, b) pSIVgag/pol/env plus the control plasmid and c) a 3rd group of 8 will receive control plasmids
only. All animals will be inoculated by the rectal route with pathogenic SIVmac251. Materials will be
provided to investigators at the TNPRC, University of Pennsylvania (UPenn) and UAB. This aim is expanded
to 8 animals per group to increase the statistical power of the experiment.
开发有效的艾滋病疫苗仍然是艾滋病毒研究的最高优先事项之一。
因为越来越多的证据表明有效的疫苗需要体液和细胞
免疫,这个 HIV-RAD 项目建议使用以下方法诱导和测量细胞和体液免疫
质粒 DMA 构建表达 SIV gag、-pol-env 基因以及新型趋化因子 DNA 质粒以解决
粘膜细胞免疫和体液免疫。该提案描述了一种诱导系统性和
粘膜免疫。项目 #3 的总体目标是评估肌内 (IM) 的潜力
递送趋化因子以增强 SIVmac 模型中的粘膜免疫。要检验的假设是
趋化因子诱导粘膜归巢免疫细胞重定向至全身区室
导致细胞和体液粘膜免疫反应而无需粘膜免疫。
将测试粘膜表达的趋化因子 CTACK、MECK、TECK 的个体潜力
增强系统性 SIV DNA 疫苗的粘膜免疫反应。疫苗接种
该方法将使用优化的 SIVgag/pol/env 加上每种质粒形式对猕猴进行 IM 联合免疫
粘膜表达的趋化因子。具体目标是:
1 A. 系统性地测量血液和体液中抗原特异性细胞介导的免疫反应
恒河猴肌内质粒与 3 种趋化因子联合免疫后的粘膜
加上 pSIVgag/pol/env。这一目标扩大到每组测试 5 只猴子,而实验中每组只测试 3 只猴子。
之前提交的内容。
1B.系统地测量血液和淋巴液中抗原特异性抗体介导的免疫反应
恒河猴与个体进行 IM 联合免疫后的淋巴结组织以及粘膜中
趋化因子加上 pSIVgag/pol/env。 1A中的动物样本也将提供给大学
由 Jiri Mestecky 博士领导的阿拉巴马伯明翰 (DAB) 小组。
2. 使用SIVmac-rhesus模型进行动物功效研究,以评估a) 1种选定的趋化因子
佐剂,b) pSIVgag/pol/env 加上对照质粒,c) 第三组 8 个将接受对照质粒
仅有的。所有动物都将通过直肠途径接种致病性 SIVmac251。材料将是
提供给 TNPRC、宾夕法尼亚大学 (UPenn) 和 UAB 的研究人员。这个目标扩大了
每组8只动物以增加实验的统计功效。
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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Preston A Marx其他文献
Frag-Virus: a new term to distinguish presumptive viruses known primarily from sequence data
- DOI:
10.1186/1743-422x-5-34 - 发表时间:
2008-02-27 - 期刊:
- 影响因子:3.800
- 作者:
Alexander Voevodin;Preston A Marx - 通讯作者:
Preston A Marx
Prevalence of HIV-2 and ART treatment coverage in Northern Sierra Leone
- DOI:
10.1186/1471-2334-14-s2-p15 - 发表时间:
2014-05-23 - 期刊:
- 影响因子:3.000
- 作者:
Nell G Bond;Augustine Goba;Danielle Levy;Lina M Moses;Sallieu K Sesay;Idriss Bangura;Matthew Kemoh Gibateh;Sheik H Khan;Preston A Marx - 通讯作者:
Preston A Marx
Serial passage of HIV-2F: a pigtail macaque model for HIV emergence
- DOI:
10.1186/1471-2334-14-s2-p57 - 发表时间:
2014-05-23 - 期刊:
- 影响因子:3.000
- 作者:
Nell G Bond;Stephanie L Feely;Christopher Monjure;Michael Lauck;David O’Connor;Nick Manness;Preston A Marx - 通讯作者:
Preston A Marx
Preston A Marx的其他文献
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{{ truncateString('Preston A Marx', 18)}}的其他基金
DNA VACCINE FOR INDUCTION OF MUCOSAL IMMUNITY
用于诱导粘膜免疫的 DNA 疫苗
- 批准号:
8358091 - 财政年份:2011
- 资助金额:
$ 22.05万 - 项目类别:
HIGHLY EFFECTIVE CONTROL OF AIDS VIRUS CHALLENGE IN MACAQUES
高效控制猕猴中的艾滋病病毒挑战
- 批准号:
8358058 - 财政年份:2011
- 资助金额:
$ 22.05万 - 项目类别:
EFFICACY AND TOXICITY OF CSIC AND RETROCYCLIN IN THE SIV VAGINAL CHALLENGE MODEL
CSIC 和逆环素在 SIV 阴道挑战模型中的功效和毒性
- 批准号:
8358131 - 财政年份:2011
- 资助金额:
$ 22.05万 - 项目类别:
PATHOGENESIS OF NATURAL SIV AND STLV INFECTIONS IN HUMANS
人类自然 SIV 和 STLV 感染的发病机制
- 批准号:
8358130 - 财政年份:2011
- 资助金额:
$ 22.05万 - 项目类别:
NHP PILOT STUDY OF A NOVEL PROTEIN ADJUVANT FOR VACCINES AGAINST HUMAN PATHOGENS
NHP 针对人类病原体疫苗的新型蛋白质佐剂的试点研究
- 批准号:
8358134 - 财政年份:2011
- 资助金额:
$ 22.05万 - 项目类别:
DNA VACCINE FOR INDUCTION OF MUCOSAL IMMUNITY
用于诱导粘膜免疫的 DNA 疫苗
- 批准号:
8172993 - 财政年份:2010
- 资助金额:
$ 22.05万 - 项目类别:
EFFICACY AND TOXICITY OF CSIC AND RETROCYCLIN IN THE SIV VAGINAL CHALLENGE MODEL
CSIC 和逆环素在 SIV 阴道挑战模型中的功效和毒性
- 批准号:
8173044 - 财政年份:2010
- 资助金额:
$ 22.05万 - 项目类别:
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