Potent immune response against HIV-1 and protection from virus challenge in hu-PBL-SCID mice immunized with inactivated virus-pulsed dendritic cells generated in the presence of IFN-alpha.

Potent immune response against HIV-1 and protection from virus challenge in hu-PBL-SCID mice immunized with inactivated virus-pulsed dendritic cells generated in the presence of IFN-alpha.
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DOI:
10.1084/jem.20021924
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发表时间:
2003-07-21
期刊:
The Journal of experimental medicine
影响因子:
--
通讯作者:
Belardelli F
Belardelli F
中科院分区:
其他
文献类型:
--
作者:
Lapenta C;Santini SM;Logozzi M;Spada M;Andreotti M;Di Pucchio T;Parlato S;Belardelli F

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艾滋病研究的一个主要挑战是开发能够诱导针对HIV-1的免疫应答的体液和细胞臂的治疗性疫苗策略。在这项工作中,我们评估了用醛硫醇-2灭活的HIV-1脉冲的DC在用人PBL重建的SCID小鼠(hu-PBL-SCID小鼠)中诱导保护性抗病毒人免疫应答的能力。用单核细胞暴露于GM-CSF/IFN-α(IFN-DCs)后产生的DCs免疫hu-PBL-SCID小鼠,并用灭活的HIV-1脉冲,导致人抗HIV-1抗体的显著诱导,这与血清中抗HIV中和活性的检测相关。通过IFN-γ Elispot分析测定,该疫苗接种方案还促进了针对HIV-1的人CD 8 + T细胞应答的产生。值得注意的是,当用抗原脉冲的IFN-DC免疫的hu-PBL-SCID小鼠感染HIV-1时,与对照动物相比,观察到病毒感染的抑制。这些结果表明,IFN-DCs与灭活的HIV-1脉冲可以代表一个有价值的方法免疫干预HIV-1感染的患者。
A major challenge of AIDS research is the development of therapeutic vaccine strategies capable of inducing the humoral and cellular arms of the immune responses against HIV-1. In this work, we evaluated the capability of DCs pulsed with aldrithiol-2–inactivated HIV-1 in inducing a protective antiviral human immune response in SCID mice reconstituted with human PBL (hu-PBL-SCID mice). Immunization of hu-PBL-SCID mice with DCs generated after exposure of monocytes to GM-CSF/IFN-α (IFN-DCs) and pulsed with inactivated HIV-1 resulted in a marked induction of human anti–HIV-1 antibodies, which was associated with the detection of anti-HIV neutralizing activity in the serum. This vaccination schedule also promoted the generation of a human CD8+ T cell response against HIV-1, as measured by IFN-γ Elispot analysis. Notably, when the hu-PBL-SCID mice immunized with antigen-pulsed IFN-DCs were infected with HIV-1, inhibition of virus infection was observed as compared with control animals. These results suggest that IFN-DCs pulsed with inactivated HIV-1 can represent a valuable approach of immune intervention in HIV-1–infected patients.
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