Immunology Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland; Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland.
Gastroenterology. 2013 Nov;145(5):1026-34. doi: 10.1053/j.gastro.2013.07.044. Epub 2013 Jul 31.
BACKGROUND & AIMS: Infection with hepatitis B virus (HBV) can be prevented by vaccination with HB surface (HBs) antigen, which induces HBs-specific antibodies and T cells. However, the duration of vaccine-induced protective immunity is poorly defined for health care workers who were vaccinated as adults.
We investigated the immune mechanisms (antibody and T-cell responses) of long-term protection by the HBV vaccine in 90 health care workers with or without occupational exposure to HBV, 10-28 years after vaccination.
Fifty-nine of 90 health care workers (65%) had levels of antibodies to HBs antigen above the cut-off (>12 mIU/mL) and 30 of 90 (33%) had HBs-specific T cells that produced interferon-gamma. Titers of antibodies to HBs antigen correlated with numbers of HBs-specific interferon-gamma-producing T cells, but not with time after vaccination. Although occupational exposure to HBV after vaccination did not induce antibodies to the HBV core protein (HBcore), the standard biomarker for HBV infection, CD4(+) and CD8(+) T cells against HBcore and polymerase antigens were detected. Similar numbers of HBcore- and polymerase-specific CD4(+) and CD8(+) T cells were detected in health care workers with occupational exposure to HBV and in patients who acquired immunity via HBV infection. Most of the HBcore- and polymerase-specific T cells were CD45RO(+)CCR7(-)CD127(-) effector memory cells in exposed health care workers and in patients with acquired immunity. In contrast, most of the vaccine-induced HBs-specific T cells were CD45RO(-)CCR7(-)CD127(-) terminally differentiated cells.
HBs antigen vaccine-induced immunity protects against future infection but does not provide sterilizing immunity, as evidenced by HBcore- and polymerase-specific CD8(+) T cells in vaccinated health care workers with occupational exposure to HBV. The presence of HBcore- and HBV polymerase-specific T-cell responses is a more sensitive indicator of HBV exposure than detection of HBcore-specific antibodies.
乙型肝炎病毒(HBV)感染可以通过接种乙型肝炎表面抗原(HBs)疫苗来预防,该疫苗可诱导 HBs 特异性抗体和 T 细胞。然而,对于成年时接种疫苗的医护人员,疫苗诱导的保护性免疫持续时间尚不清楚。
我们调查了 90 名医护人员(有或无乙型肝炎病毒职业暴露)在接种疫苗 10-28 年后,HBV 疫苗的长期保护免疫机制(抗体和 T 细胞反应)。
90 名医护人员中,有 59 名(65%)的 HBs 抗原抗体水平高于临界值(>12 mIU/mL),有 30 名(33%)的 HBs 特异性 T 细胞产生了干扰素-γ。HBs 抗原抗体的滴度与 HBs 特异性产生干扰素-γ的 T 细胞数量相关,但与接种疫苗后的时间无关。尽管接种疫苗后职业性接触 HBV 不会诱导乙型肝炎核心抗原(HBcore)抗体,HBcore 是乙型肝炎病毒感染的标准标志物,但检测到针对 HBcore 和聚合酶抗原的 CD4+和 CD8+T 细胞。在有 HBV 职业接触的医护人员和通过 HBV 感染获得免疫力的患者中,检测到的 HBcore 和聚合酶特异性 CD4+和 CD8+T 细胞数量相似。在有职业性接触 HBV 的医护人员和获得免疫力的患者中,大多数 HBcore 和聚合酶特异性 T 细胞是 CD45RO+CCR7-CD127-CD127-效应记忆细胞。相比之下,大多数 HBs 特异性 T 细胞是 CD45RO-CCR7-CD127-CD127-终末分化细胞。
HBs 抗原疫苗诱导的免疫可预防未来的感染,但不能提供绝育免疫,这可以从有 HBV 职业接触的接种疫苗的医护人员中检测到 HBcore 和聚合酶特异性 CD8+T 细胞得到证明。HBcore 和 HBV 聚合酶特异性 T 细胞反应的存在是 HBV 暴露的比 HBcore 特异性抗体检测更敏感的指标。