Fazle Akbar Sk Md, Furukawa Shinya, Yoshida Osamu, Hiasa Yoichi, Horiike Norio, Onji Morikazu
Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon City, Ehime 791-0295, Japan.
J Hepatol. 2007 Jul;47(1):60-6. doi: 10.1016/j.jhep.2007.02.021. Epub 2007 Apr 9.
BACKGROUND/AIMS: Antigen-pulsed dendritic cells (DCs) are now used for treatment of patients with cancers, however, the efficacy of these DCs has never been evaluated for prophylactic purposes. The aim of this study was (1) to prepare hepatitis B surface antigen (HBsAg)-pulsed human blood DCs, (2) to assess immunogenicity of HBsAg-pulsed DCs in vitro and (3) to evaluate the efficacy of HBsAg-pulsed DCs in hepatitis B (HB) vaccine nonresponders.
Human peripheral blood DCs were cultured with HBsAg to prepare HBsAg-pulsed DCs. The expression of immunogenic epitopes of HBsAg on HBsAg-pulsed DCs was assessed in vitro. Finally, HBsAg-pulsed DCs were administered, intradermally to six HB vaccine nonresponders and the levels of antibody to HBsAg (anti-HBs) in the sera were assessed.
HB vaccine nonresponders did not exhibit features of immediate, early or delayed adverse reactions due to administration of HBsAg-pulsed DCs. Anti-HBs were detected in the sera of all HB vaccine nonresponders within 28 days after administration of HBsAg-pulsed DCs.
This study opens a new field of application of antigen-pulsed DCs for prophylactic purposes when adequate levels of protective antibody cannot be induced by traditional vaccination approaches.
背景/目的:抗原脉冲树突状细胞(DCs)目前用于癌症患者的治疗,然而,这些DCs在预防方面的疗效从未被评估过。本研究的目的是:(1)制备乙肝表面抗原(HBsAg)脉冲的人血DCs;(2)在体外评估HBsAg脉冲DCs的免疫原性;(3)评估HBsAg脉冲DCs对乙肝(HB)疫苗无应答者的疗效。
将人外周血DCs与HBsAg共同培养以制备HBsAg脉冲DCs。在体外评估HBsAg脉冲DCs上HBsAg免疫原性表位的表达。最后,将HBsAg脉冲DCs皮内注射给6名HB疫苗无应答者,并评估血清中乙肝表面抗原抗体(抗-HBs)的水平。
HB疫苗无应答者未表现出因注射HBsAg脉冲DCs而出现的即刻、早期或延迟不良反应。在注射HBsAg脉冲DCs后28天内,所有HB疫苗无应答者的血清中均检测到抗-HBs。
当传统疫苗接种方法无法诱导出足够水平的保护性抗体时,本研究为抗原脉冲DCs在预防方面的应用开辟了一个新领域。