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.
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。