Long-lasting humoral immune response induced in HIV-1-infected patients by a synthetic peptide (AT20) derived from the HIV-1 matrix protein p17 functional epitope.

Q2 Medicine HIV Clinical Trials Pub Date : 2015-08-01 Epub Date: 2015-06-09 DOI:10.1179/1528433614Z.0000000018
Emanuele Focà, Maria Luisa Iaria, Francesca Caccuri, Simona Fiorentini, Davide Motta, Cinzia Giagulli, Francesco Castelli, Arnaldo Caruso
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引用次数: 2

Abstract

Objective: A therapeutic vaccination based on a synthetic peptide (AT20) representative of the HIV-1 matrix protein p17 (p17) functional region, coupled to keyhole limpet hemocyanin (KLH) AT20-KLH was capable of inducing the production of high-avidity antibodies (Abs) toward a previous untargeted p17 hotspot of functional activity in highly active antiretroviral therapy (HAART)-treated HIV-1-infected patients. Since avidity of Abs after immunization and the retention of antigens are important in sustaining the long-lasting production of specific humoral responses, we asked whether AT20-KLH vaccination would result in development of a long-lived immune response.

Methods: The long-term duration of Ab response to AT20-KLH has been evaluated in 10 patients previously enrolled for the AT20-KLH vaccination trial at day 898 post-immunization. Ab titer and their avidity was assessed using specifically designed ELISA assays, whereas their neutralizing capacity was estimated in vitro using a 'wound sealing assay'.

Results: Data obtained show that high titers of specific anti-AT20 Abs were maintained at more than 2 years after the last immunization. Furthermore, these Abs were capable to neutralize exogenous p17, as assessed by ability of sera derived from AT20-KLH-immunized patients to block the ability of p17 to promote cell migration in vitro.

Conclusion: This finding attests for a successful AT20-KLH vaccine molecule formulation and for an effective HAART-dependent Ab persistence.

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由HIV-1基质蛋白p17功能表位衍生的合成肽(AT20)诱导HIV-1感染患者的持久体液免疫反应
目的:一种基于代表HIV-1基质蛋白p17 (p17)功能区的合成肽(AT20)的治疗性疫苗,与锁孔帽皮血青蛋白(KLH) AT20-KLH偶联,能够在高效抗逆转录病毒疗法(HAART)治疗的HIV-1感染患者中诱导产生针对先前非靶向p17功能活性热点的高亲和力抗体(Abs)。由于免疫后抗体的亲和力和抗原的保留对于维持特异性体液反应的长期产生很重要,我们想知道AT20-KLH疫苗接种是否会导致长期免疫反应的发展。方法:在接种AT20-KLH疫苗后第898天,对10名患者进行了AT20-KLH疫苗接种试验,评估了抗体对AT20-KLH的长期反应时间。使用专门设计的ELISA测定法评估抗体滴度和亲和力,而在体外使用“伤口密封测定法”评估其中和能力。结果:获得的数据显示,特异性抗at20抗体在最后一次免疫后2年以上仍保持高滴度。此外,这些抗体能够中和外源性p17,通过at20 - klh免疫患者的血清在体外阻断p17促进细胞迁移的能力来评估。结论:这一发现证明了AT20-KLH疫苗分子制剂的成功和haart依赖性Ab的有效持久性。
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来源期刊
HIV Clinical Trials
HIV Clinical Trials 医学-传染病学
CiteScore
1.76
自引率
0.00%
发文量
0
审稿时长
>12 weeks
期刊介绍: HIV Clinical Trials is devoted exclusively to presenting information on the latest developments in HIV/AIDS clinical research. This journal enables readers to obtain the most up-to-date, innovative research from around the world.
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