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一项纵向乙肝疫苗队列研究表明,尽管针对乙肝表面抗原的抗体消失,但乙肝病毒(HBV)细胞免疫仍具有持久性。

A Longitudinal Hepatitis B Vaccine Cohort Demonstrates Long-lasting Hepatitis B Virus (HBV) Cellular Immunity Despite Loss of Antibody Against HBV Surface Antigen.

作者信息

Simons Brenna C, Spradling Philip R, Bruden Dana J T, Zanis Carolyn, Case Samantha, Choromanski Tammy L, Apodaca Minjun, Brogdon Hazel D, Dwyer Gaelen, Snowball Mary, Negus Susan, Bruce Michael G, Morishima Chihiro, Knall Cindy, McMahon Brian J

机构信息

Liver Disease and Hepatitis Program, Alaska Native Tribal Health Consortium Arctic Investigations Program, Division of Preparedness and Emerging Infections, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention (CDC) WWAMI School of Medical Education, College of Health, University of Alaska Anchorage.

Division of Viral Hepatitis, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, CDC, Atlanta, Georgia.

出版信息

J Infect Dis. 2016 Jul 15;214(2):273-80. doi: 10.1093/infdis/jiw142. Epub 2016 Apr 7.

Abstract

BACKGROUND

Long-lasting protection resulting from hepatitis B vaccine, despite loss of antibody against hepatitis B virus (HBV) surface antigen (anti-HBs), is undetermined.

METHODS

We recruited persons from a cohort vaccinated with plasma-derived hepatitis B vaccine in 1981 who have been followed periodically since. We performed serological testing for anti-HBs and microRNA-155 and assessed HBV-specific T-cell responses by enzyme-linked immunospot and cytometric bead array. Study subgroups were defined 32 years after vaccination as having an anti-HBs level of either ≥10 mIU/mL (group 1; n = 13) or <10 mIU/mL (group 2; n = 31).

RESULTS

All 44 participants, regardless of anti-HBs level, tested positive for tumor necrosis factor α, interleukin 10, or interleukin 6 production by HBV surface antigen-specific T cells. The frequency of natural killer T cells correlated with the level of anti-HBs (P = .008). The proportion of participants who demonstrated T-cell responses to HBV core antigen varied among the cytokines measured, suggesting some natural exposure to HBV in the study group. No participant had evidence of breakthrough HBV infection.

CONCLUSIONS

Evidence of long-lasting cellular immunity, regardless of anti-HBs level, suggests that protection afforded by primary immunization with plasma-derived hepatitis B vaccine during childhood and adulthood lasts at least 32 years.

摘要

背景

乙肝疫苗所产生的长期保护作用,尽管针对乙肝病毒(HBV)表面抗原(抗-HBs)的抗体消失,但仍未明确。

方法

我们从1981年接种血浆源性乙肝疫苗的队列中招募人员,自那时起对其进行定期随访。我们对抗-HBs和微小RNA-155进行了血清学检测,并通过酶联免疫斑点法和细胞计数微球阵列评估了HBV特异性T细胞反应。在接种疫苗32年后,研究亚组被定义为抗-HBs水平≥10 mIU/mL(第1组;n = 13)或<10 mIU/mL(第2组;n = 31)。

结果

所有44名参与者,无论抗-HBs水平如何,HBV表面抗原特异性T细胞产生肿瘤坏死因子α、白细胞介素10或白细胞介素6的检测均呈阳性。自然杀伤T细胞的频率与抗-HBs水平相关(P = .008)。在所检测的细胞因子中,对HBV核心抗原表现出T细胞反应的参与者比例各不相同,这表明研究组中存在一些自然感染HBV的情况。没有参与者有突破性HBV感染的证据。

结论

无论抗-HBs水平如何,长期细胞免疫的证据表明,儿童期和成年期接种血浆源性乙肝疫苗所提供的保护作用至少持续32年。

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