Department of Epidemiology and Biostatistics, Xi'an Jiaotong University College of Medicine, Xi'an, Shaanxi 710061, PR China.
Vaccine. 2011 Mar 9;29(12):2302-7. doi: 10.1016/j.vaccine.2011.01.025. Epub 2011 Jan 28.
The duration of protection of hepatitis B vaccine remains incompletely understood. To assess the long-term protection provided by a primary vaccine series, the current study again recruited all subjects of a previous randomized placebo-controlled trial cohort 23 years after vaccination. Two hundred and sixty-one healthy children aged 5-9 years living in a highly HBV-endemic country were enrolled in the primary trial and received three doses of plasma-derived vaccine or placebo. The primary placebo receivers who did not receive any immunization against hepatitis B were used as non-vaccinated controls in the current study. After eliminating the interference of an early booster dose and vaccines outside the study, 48.1% (39/81) vaccinees still maintained anti-HBs titers ≥ 10 mI U/mL at Year 23, higher than 34.7% (26/75) in non-vaccinated controls (P=0.088). 75-100% of vaccinees with anti-HBs titer <10 mI U/mL at Year 23 in different sub-groups divided according to early immune backgrounds developed a rapid and robust antibody anamnestic response after a booster dose, highly significantly different from non-vaccinated controls who received the same dose of vaccine (7.5%, P<0.01). No case of clinically significant HBV infection was found in the primary cohort during the whole 23 years, but 10 transient HBsAg seroconversions in the primary placebo group and one in the primary vaccine group were determined. Anti-HBc positive rate obviously tended to be lower in vaccinees compared with non-vaccinated controls at Year 23. These results suggest a persisting immune memory and certain protection for 23 years after primary vaccination in children living in highly HBV-endemic areas. Clinically insignificant infections, which cannot be avoided and may often occur in vaccinees, play a positive role in the maintaining of immunity to HBV. Booster doses should be unnecessary for more than 20 years after a full primary immunization in children (as catch-up vaccination) and, also likely, in newborns living in highly HBV-endemic areas.
乙肝疫苗的保护持续时间仍不完全清楚。为了评估初免系列疫苗提供的长期保护作用，本研究再次对 23 年前接种过疫苗的一项随机安慰剂对照试验队列的所有受试者进行了招募。261 名居住在乙型肝炎病毒高度流行国家的 5-9 岁健康儿童参与了初免试验，接受了 3 剂血源性疫苗或安慰剂。本研究中，将初免安慰剂接受者作为未接种乙肝疫苗的非接种对照。在消除早期加强剂量和研究之外疫苗的干扰后，48.1%（39/81）的疫苗接种者在第 23 年仍保持抗-HBs 滴度≥10mIU/mL，高于未接种对照者的 34.7%（26/75）（P=0.088）。根据早期免疫背景，在根据不同亚组划分的第 23 年抗-HBs 滴度<10mIU/mL 的疫苗接种者中，75-100%的人在加强剂量后产生了快速和强大的抗体回忆反应，与接受相同剂量疫苗的非接种对照者高度显著不同（7.5%，P<0.01）。在整个 23 年期间，初免队列中未发现有临床意义的乙型肝炎病毒感染病例，但在初免安慰剂组中发现了 10 例短暂性 HBsAg 血清转换，初免疫苗组中发现了 1 例。与非接种对照者相比，第 23 年时疫苗接种者的抗-HBc 阳性率明显较低。这些结果表明，在乙型肝炎病毒高度流行地区的儿童中，初免接种后 23 年仍存在持续的免疫记忆和一定的保护作用。在疫苗接种者中，无法避免且可能经常发生的临床无意义感染，在维持对乙型肝炎病毒的免疫方面发挥了积极作用。在儿童（作为补种）和可能也在乙型肝炎病毒高度流行地区的新生儿中，在完成初免免疫后 20 年以上可能不需要加强剂量。
