英语晨读 ·
山东省立医院疼痛科英语晨读已经坚持10余年的时间了，每天交班前15分钟都会精选一篇英文文献进行阅读和翻译。一是可以保持工作后的英语阅读习惯，二是可以学习前沿的疼痛相关知识。我们会将晨读内容与大家分享，助力疼痛学习。
本次文献选自Sly JR, Harris AL. Recombinant Zoster Vaccine (Shingrix) to Prevent Herpes Zoster. Nurs Womens Health. 2018;22(5):417-422.
Mechanism of Action
Immunity occurs through natural and specific acquired cellular responses. Natural immunity uses the skin as a barrier, as well as phagocytes and natural killer cells to protect the body.Specific immunity uses cell-mediated or humoral responses.
When a foreign virus such as HZ is present, the body recog-nizes it as an antigen. Cellular-mediated responses will target HZ using T cells (CD4 helper T cells and CD8 cytotoxic T cells) and macrophages. Humoral-mediated responses will develop antibodies to target HZ. Antibodies, which are structurally related to glycoproteins (also known as immunoglobulins), are produced from B lymphocytes to recognize and bind to anti-gens (Burchum & Rosenthal, 2016). HZ-specific T-cell–medi-ated immunity decreases with drugs that compromise immunity (e.g., high-dose glucocorticoids and antineoplastic agents) or with diseases that compromise immunity. It also wanes with increasing age. This decreasing immunity leaves the most vulnerable population at risk for the surfacing of HZ and the resulting painful postherpetic neuralgia.
作用机理
机体免疫可以分为自然免疫和特异性免疫两部分。自然免疫利用皮肤作为屏障，以及吞噬细胞和自然杀伤细胞来保护人体。特异性免疫通过细胞介导或体液免疫应答来实现。当一种外来病毒如HZ出现时，人体会将其识别为抗原。细胞介导的免疫应答将利用T细胞（CD4辅助T细胞和CD8细胞毒性T细胞）和巨噬细胞靶向HZ。体液介导的免疫应答会产生针对HZ的抗体。B淋巴细胞产生的抗体能够识别和结合抗原，这些抗体在结构上与糖蛋白（也称为免疫球蛋白）相关。如果使用了降低免疫力的药物（如大剂量糖皮质激素和抗肿瘤药物）或患有导致免疫力下降的疾病，则针对HZ的特异性T细胞介导的免疫力也会随之降低。随着年龄的增长，免疫力也会减弱。这种免疫力的下降使易感人群面临HZ的风险和由此产生的带状疱疹后遗神经痛的风险。
Live and non-live vaccines have been developed to give exogenous protection from HZ virus infection. T-cell–mediated immunity is necessary to maintain the latency, and, as described, these responses decline with age or immune suppression. Therefore, testing for past varicella infection is not useful when considering immunization for older adults (CDC, 2018a). A better approach to preventing HZ Q4 would be to boost the immunity to be greater than the latency threshold (Weinberg & Levin, 2010).
活疫苗和灭活疫苗已被研制出来，以提供外源性保护，使人们免受HZ病毒感染。T细胞介导的免疫是维持病毒处于持续休眠状态所必需的，而且，如前所述，这些反应会随着年龄或免疫抑制而下降。因此，在考虑对老年人进行免疫接种时，检测过去的水痘感染是没有用的。一个更好的预防HZ的方法是提高免疫力，使其能够将病毒压制在休眠状态而不能激活。
The live zoster vaccine (Zostavax), which was licensed in 2006, contains live attenuated VZVs that raise the cell-mediated immunity. Although it has reduced the disease burden, its efficacy has been questioned as inferior to the non-live shingles vaccine (Cunningham et al., 2016; Dooling,Guo, Leung, Belongia, & Harpaz, 2017). Shingrix, the non-live vaccine, was shown to boost VZV-specific immune response,which is thought to be the mechanism by which it protects against zoster disease (U.S. FDA, 2017). It stimulates active immunity and contains recombinant VZV glycoprotein E component with an adjuvant (Sandgren, Bertram, & Cunningham, 2016). In many instances, adjuvants are added to enhance the immunogenicity of a vaccine. This enhance-ment activates, prolongs, and improves T-cell or antibody re-sponses to the vaccine (Edmunds & Mayhew, 2016;Sandgren, Bertram, & Cunningham, 2016).
疱疹活疫苗（Zostavax）于2006年获得许可，它含有带状疱疹病毒的减毒活疫苗，能够提高细胞介导免疫应答。尽管它降低了患病风险，但其疗效被质疑不如灭活带状疱疹疫苗。灭活疫苗Shingrix能够激活带状疱疹病毒特异性的免疫应答，这被认为是其能够有效保护机体免受带状疱疹侵害的机制。它激活主动免疫过程，并含有带有佐剂的重组VZV糖蛋白E成分。在许多情况下，添加佐剂是为了增强疫苗的免疫原性。从而激活、延长和改善T细胞或抗体对疫苗的反应。
Efficacy, Safety, and Cost
Although effective against HZ, the use of Zostavax showed decreasing immunity with advanced age and over time. For this reason, Phase I and II trials were conducted to improve immunity using Shingrix, which combines an antigen, glycoprotein E, and an adjuvant (ASO1B). Clinical trial results showed efficacious cellular and humoral responses in older adults with immunity that persisted over a 3-year period. The vaccine also proved to be safe. A Phase III, two-part multicenter clinical trial with more than 30,000 participants was conducted to evaluate the efficacy of RZV. Participants were randomized 1:1 to receive RZV or placebo. Results showed that the vaccine was 96.6% effective in preventing HZ among individuals 50 to 59 years old and 97.4% effective in those 60 to 69 years old. Using pooled data from both study arms, researchers found RZV to be 91.3% effective in preventing HZ among participants ages 70 years and older. After 1 year, RZV was found to be 97.6% effective, falling to 84.7% effective among individuals ages 70 years and older in the following 3 years of the study. Lal et al. evaluated the safety and efficacy of RZV and found an overall efficacy of 97.2%. This efficacy did not wane with the older cohorts.
功效、安全性和成本
虽然Zostavax对HZ有效，但随着年龄的增长和时间的推移， Zostavax的免疫能力会逐渐降低。基于这个原因，一期和二期临床试验使用结合了抗原、糖蛋白E和佐剂（ASO1B）的Shingrix疫苗来提高免疫能力。临床试验结果显示，Shingrix在老年人群中产生了有效的细胞和体液免疫应答，免疫能力持续了3年以上。该疫苗的安全性也被证实。一项包含两部分的多中心三期临床试验，共有30000多名参与者，以评估RZV的疗效。受试者按1:1随机分组，接受RZV或安慰剂。结果表明，该疫苗对50～59岁人群的预防效果为96.6%，对60～69岁人群的预防效果为97.4%。综合两个研究组的数据，研究人员发现，在70岁及以上的参与者中，RZV对预防HZ的有效率为91.3%。研究发现在70岁及以上人群中，接种疫苗1年后， RZV的预防有效率为97.6%，3年后该有效率降至84.7%。Lal等人评价了RZV的安全性和有效性，总有效率为97.2%。并且这种有效率并没有随着年龄的增长而减弱。
The safety of HZ recombinant subunit vaccine with an adjuvant was reassuring. No significant difference was noted between the HZ recombinant subunit with adjuvant and the placebo group. Of the reactions described by Lal et al., site reactions were most common, with systemic complaints including pain and myalgia lasting 1 to 3 days.
带有佐剂的HZ重组亚单位疫苗的安全性令人放心。其安全性与安慰剂组无显著性差异。根据Lal等人的描述，局部反应最为常见，全身反应一般为疼痛和肌痛，大约持续1至3天。
Costs of the two vaccines are similar (see Table 1). The full price of Shingrix is $280.00 for the two-dose series, compared with $213.00 for the single dose of Zostavax (Umansky, 2018). Shingrix is covered by Medicare Part D and by most private insurance plans (CDC, 2018c). However, consumers may be required to pay a co-payment, which is plan dependent. For individuals who are uninsured, GlaxoSmithKline offers a patient assistance program for registered providers. A specific application must be submitted.
两种疫苗的成本相似（见表1）。Shingrix两剂的全价为280.00美元，而Zostavax的单剂价格为213.00美元。Shingrix在医疗保险D和大多数商业保险计划报销范围内。然而，消费者可能需要支付部分费用，这取决于医保类型。对于未参保的个人，葛兰素史克为注册医疗机构提供患者援助计划。必须提交具体申请。
| 表一：SHINGRIX与ZOSTAVAX预防带状疱疹的比较 | ||
| 特征 | Shingrix | Zostavax |
| 主动免疫 | 灭活的重组水痘带状疱疹病毒，糖蛋白E组分与佐剂 | 减毒水痘带状疱疹病毒 |
| 剂量 | 两次（第一次给药后2-6个月第二次给药） | 一次 |
| 推荐年龄 | 50岁及以上 | 60岁及以上（FDA批准50岁及以上） |
| 功效 | >90% | 51% |
| 制造商 | 葛兰素史克 | 默克夏普公司 |
| 成本 | 280美元/两剂 | 213美元 |
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