West D J, Calandra G B
Merck Research Laboratories, West Point, PA 19486, USA.
Vaccine. 1996 Aug;14(11):1019-27. doi: 10.1016/0264-410x(96)00062-x.
This paper reviews published literature on the long-term persistence of immunologic memory for HBsAg after a course of hepatitis B vaccine and the functional significance this has for policy on booster vaccination. Several studies have shown that vaccine induced antibody (anti-HBs) specific for the surface antigen (HBsAg) of hepatitis B virus (HBV) is protective at a serum concentration of 10 milli-International Units per milliliter (mIU ml-1). When acquired passively (e.g. from hepatitis B immune globulin), susceptibility to infection returns as antibody declines. However, vaccine induces active synthesis of anti-HBs accompanied by immunologic memory for HBsAg that affords ongoing protection independent of antibody. Persistent memory over periods of 5 years or more is evident from large, rapid increases in antibody following booster vaccination, even in subjects who have lost antibody. Complementary studies, using an in vitro enzyme linked immunosorbent assay (spot-ELISA), show that the number of memory B lymphocytes able to produce anti-HBs does not diminish as the level of antibody declines. That immunologic memory provides effective immunity is suggested by serologic studies over periods of 5 years or more of vaccinees frequently exposed to HBV. Although many failed to maintain at least 10 mIU ml-1 of antibody, there have been very few clinically significant breakthrough infections. Thus, it appears unnecessary to give healthy vaccinees a booster vaccination when the level of anti-HBs falls below 10 mIU ml-1. Current studies suggest good retention of immunologic memory in healthy vaccinees over periods of 5-12 years. While additional studies will better define the limits of this phenomenon, routine booster vaccination should not be needed to sustain immunologic memory and protection within 5 years and perhaps longer after the primary vaccination series.
本文综述了已发表的关于乙肝疫苗接种后乙肝表面抗原（HBsAg）免疫记忆的长期持续性及其对加强免疫接种政策的功能意义的文献。多项研究表明，针对乙肝病毒（HBV）表面抗原（HBsAg）的疫苗诱导抗体（抗-HBs）在血清浓度为每毫升10毫国际单位（mIU/ml）时具有保护作用。当被动获得（如从乙肝免疫球蛋白）时，随着抗体下降，感染易感性会恢复。然而，疫苗诱导抗-HBs的主动合成并伴有对HBsAg的免疫记忆，从而提供独立于抗体的持续保护。即使在已失去抗体的受试者中，加强免疫接种后抗体大幅快速增加，这表明5年或更长时间内存在持续的记忆。使用体外酶联免疫吸附测定（斑点酶联免疫吸附测定，spot-ELISA）的补充研究表明，随着抗体水平下降，能够产生抗-HBs的记忆B淋巴细胞数量并未减少。经常接触HBV的疫苗接种者超过5年的血清学研究表明，免疫记忆可提供有效的免疫力。尽管许多人未能维持至少10 mIU/ml的抗体水平，但临床上具有显著意义的突破性感染却很少。因此，当抗-HBs水平降至10 mIU/ml以下时，似乎没有必要给健康的疫苗接种者进行加强免疫接种。目前的研究表明，健康的疫苗接种者在5至12年期间能很好地保留免疫记忆。虽然更多研究将更好地界定这一现象的限度，但在初次接种系列疫苗后的5年甚至更长时间内，维持免疫记忆和保护可能不需要常规加强免疫接种。
