在急性期乙型肝炎病毒复制的天真和以前接种过疫苗的血液

StephenW

Cytokine and Chemokine Responses in the Acute Phase of Hepatitis B Virus Replication in Naïve and Previously Vaccinated Blood and Plasma Donors

    Sheila M. Keating1,2,#,
    John D. Heitman1,
    Shiquan Wu1,
    Xutao Deng1,2,
    Susan L. Stramer4,
    Mary C. Kuhns5,
    Carolyn Mullen5,
    Philip J. Norris1,2,3 and
    Michael P. Busch1,2

+ Author Affiliations

    1Blood Systems Research Institute, San Francisco, CA, 94118, USA
    2Department of Laboratory Medicine, University of California, San Francisco, 94143, USA
    3Department of Medicine, University of California, San Francisco, 94143, USA
    4American Red Cross, Gaithersburg, MD 20877, USA
    5Abbott Laboratories, Abbott Park, Illinois, 60064, USA

    ↵#Correspondence: Sheila M. Keating: [email protected]; Blood Systems Research Institute, San Francisco, CA; Departments of Laboratory Medicine University of California, San Francisco, CA 94118. Telephone: 1-415-265-5914. Fax: 1-415-775-3859

Abstract

Background. Blood and plasma donor screening for hepatitis B virus (HBV) DNA, HBV surface antigen (HBsAg), and antibodies to surface (anti-HBs) and core (anti-HBc) antigens allows identification of individuals who acquired HBV despite previous HBV vaccination.

Methods. Of 14 HBV acute infection donor panels (HBV-DNA-positive/anti-HBc-negative), six donors were previously vaccinated (anti-HBs+). We investigated the differences in viral kinetics and immune responses in vaccinated and non-vaccinated individuals. Serial specimens were characterized for HBV DNA and serological markers and 39 cytokines.

Results. The rate of viral load increase was blunted and virus was cleared more rapidly in vaccinated individuals (p=0.004). In unvaccinated individuals, IP-10, IL-10, MIP-1β and sIL-2Rα levels were commonly elevated at the time of peak viremia. In contrast, vaccinated individuals had earlier peaks in IL-10 and IP-10 responses that occurred at much lower viral loads and coincided with anamnestic anti-HBs responses and clearance of viremia.

Conclusion. There is earlier engagement of innate and adaptive immunity in infected subjects with previous vaccination, possibly explaining suppressed viremia in vaccine breakthrough infections. Although breakthrough infections occur in partially protected vaccine recipients, vaccination likely contributes to early control of replication, limiting immune activation and preventing development of clinically significant acute and chronic HBV infection.

    Received June 19, 2013.
    Revision received August 20, 2013.
    Accepted September 6, 2013.

    © The Author 2013. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: [email protected].

StephenW

在急性期乙型肝炎病毒复制的天真和以前接种过疫苗的血液和血浆者的细胞因子和趋化因子的响应

    希拉· Keating1 ，2 ，＃，
    约翰D. Heitman1 ，
    石泉武
    绪涛Deng1 2 ，
    苏珊L. Stramer4 ，
    的Mary C. Kuhns5 ，
    卡罗琳Mullen5
    菲利普J. Norris1 ，2,3和
    迈克尔P. Busch1 2

+作者所属机构

    血魄系统研究所，旧金山， CA ， 94118 ， USA
    2实验室医学，加州大学，旧金山， 94143 ， USA
    3医学院，加州大学，旧金山， 94143 ， USA
    4American红十字会，兰州盖瑟斯堡， MD 20877 ， USA
    雅培5Abbott实验室，公园，伊利诺伊州， 60064 ， USA

    的↵ ＃函授：希拉·基廷： [email protected]血液系统研究所，旧金山，加利福尼亚州;部门检验医学加州大学，旧金山， CA 94118 。电话： 1-415-265-5914 。传真： 1-415-775-3859

抽象

背景。 B型肝炎病毒（HBV） DNA ， HBV表面抗原（ HBsAg）的，表面的抗体（抗-HBs ）和核心抗原（抗-HBc ）血液和血浆供体筛查允许收购HBV尽管以前的乙肝疫苗的个体识别。

方法。 14 HBV急性感染捐助的面板（ HBV-DNA-positive/anti-HBc-negative ） ， 6个捐助者以前接种过（抗-HBs ） 。我们研究了病毒动力学和免疫反应的接种和未接种疫苗的个体差异。串行样品进行了表征， HBV DNA和血清学标志物和39因子。

的结果。病毒负荷增加的速率减弱，并更迅速地清除病毒接种的个体（P = 0.004 ） 。在未接种疫苗的个体中， IP -10， IL-10， MIP-1β和sIL -2Rα水平通常在病毒血症高峰时间升高。相比之下，接种疫苗的人士有更早的峰值发生在低得多的病毒载量，恰好与回忆的抗-HBs反应和清除病毒血症IL-10和IP - 10的回应。

结论。有先天和适应性免疫与以前接种的感染者，可能解释抑制病毒血症疫苗的突破感染的早期干预。虽然突破感染发生在部分保护的疫苗接种者，接种疫苗可能有助于早期控制的复制，免疫激活限制，防止临床显着的急性和慢性HBV感染者发展。

    2013年6月19日。
    修订2013年8月20日收到。
    接受2013年9月6日。

    © 2013 。由牛津大学出版社出版的美国传染病学会代表。保留所有权利。的权限，请E-mail ： ： journals.permissions oup.com 。