Zostavax® 是一种 Oka/Merck 水痘带状疱疹病毒 (VZV) 减毒活疫苗冻干制剂,它是首株获准用于预防≥50 岁成人的带状疱疹 (HZ) 和带状疱疹相关后遗神经痛的疫苗。[19]Sanford M, Keating GM. Zoster vaccine (Zostavax): a review of its use in preventing herpes zoster and postherpetic neuralgia in older adults. Drugs Aging. 2010;27:159-76.http://www.ncbi.nlm.nih.gov/pubmed/20104941?tool=bestpractice.com[20]US Food and Drug Administration. Vaccines, blood and biologics: Zostavax. February 2016. http://www.fda.gov/ (last accessed 24 February 2017).http://www.fda.gov/BiologicsBloodVaccines/Vaccines/ApprovedProducts/ucm136941.htm[21]Chen N, Li Q, Zhang Y, et al. Vaccination for preventing postherpetic neuralgia. Cochrane Database Syst Rev. 2011;(3):CD007795.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD007795.pub2/fullhttp://www.ncbi.nlm.nih.gov/pubmed/21412911?tool=bestpractice.com[22]Gagliardi AM, Andriolo BN, Torloni MR, et al. Vaccines for preventing herpes zoster in older adults. Cochrane Database Syst Rev. 2016;(3):CD008858.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD008858.pub3/fullhttp://www.ncbi.nlm.nih.gov/pubmed/26937872?tool=bestpractice.com[23]Schmader KE, Levin MJ, Gnann JW Jr, et al. Efficacy, safety, and tolerability of herpes zoster vaccine in persons aged 50-59 years. Clin Infect Dis. 2012;54:922-928.http://cid.oxfordjournals.org/content/54/7/922.longhttp://www.ncbi.nlm.nih.gov/pubmed/22291101?tool=bestpractice.com [
]Can live attenuated varicela-zoster virus vaccine prevent herpes zoster in older adults?https://cochranelibrary.com/cca/doi/10.1002/cca.1404/full显示答案 该疫苗以单剂量皮下注射方式给药,可使带状疱疹病例减少 51%,带状疱疹后遗神经痛病例减少 67%,总疾病负担减少 61%。[24]Oxman MN, Levin MJ, Johnson GR, et al; Shingles Prevention Study Group. A vaccine to prevent herpes zoster and postherpetic neuralgia in older adults. N Engl J Med. 2005 Jun 2;352(22):2271-84.http://www.nejm.org/doi/full/10.1056/NEJMoa051016http://www.ncbi.nlm.nih.gov/pubmed/15930418?tool=bestpractice.com 由于它是一种活疫苗,因此禁忌将其用于严重免疫抑制者、妊娠女性或儿童。已证明此疫苗可减轻接种疫苗者以及在接种疫苗后出现带状疱疹的患者在日常生活活动中由带状疱疹带来的负担。[25]Schmader KE, Johnson GR, Saddier P, et al. Effect of a zoster vaccine on herpes zoster-related interference with functional status and health-related quality-of-life measures in older adults. J Am Geriatr Soc. 2010;58:1634-1641.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2946120/?tool=pubmedhttp://www.ncbi.nlm.nih.gov/pubmed/20863322?tool=bestpractice.com 然而,Zostavax® 疫苗对老年患者的疗效较差,疫苗效力约在 10 年后完全消失。[26]Morrison VA, Johnson GR, Schmader KE, et al; Shingles Prevention Study Group. Long-term persistence of zoster vaccine efficacy. Clin Infect Dis. 2015 Mar 15;60(6):900-9.https://academic.oup.com/cid/article/60/6/900/496651http://www.ncbi.nlm.nih.gov/pubmed/25416754?tool=bestpractice.com
2017 年,美国食品药品监督管理局 (Food and Drug Administration, FDA) 批准了一种新的带状疱疹疫苗 Shingrix®,该疫苗同样适用于年龄≥50 岁的成年人。Shingrix® 是一种重组亚单位疫苗,含有 VZV 糖蛋白 E 和 AS01B 佐剂系统。这款新疫苗需进行 2 次肌内注射剂量,第一剂后 2-6 个月接种第二剂,与 Zostavax® 相比,它的疗效得到了显著提高,可使带状疱疹病例减少 97%。[27]Lal H, Cunningham AL, Godeaux O, et al; ZOE-50 Study Group. Efficacy of an adjuvanted herpes zoster subunit vaccine in older adults. N Engl J Med. 2015 May 28;372(22):2087-96.http://www.nejm.org/doi/full/10.1056/NEJMoa1501184http://www.ncbi.nlm.nih.gov/pubmed/25916341?tool=bestpractice.com更重要的是,Shingrix® 对老年患者同样有效,其疗效在 4 年后仅略有下降。[28]Cunningham AL, Lal H, Kovac M, et al; ZOE-70 Study Group. Efficacy of the herpes zoster subunit vaccine in adults 70 years of age or older. N Engl J Med. 2016 Sep 15;375(11):1019-32.http://www.nejm.org/doi/full/10.1056/NEJMoa1603800http://www.ncbi.nlm.nih.gov/pubmed/27626517?tool=bestpractice.com 然而,关于接种 2 剂长期效力的数据不明。单剂的效力也不明,但更早期的研究表明,单剂不会产生强烈的免疫应答。[29]Chlibek R, Smetana J, Pauksens K, et al. Safety and immunogenicity of three different formulations of an adjuvanted varicella-zoster virus subunit candidate vaccine in older adults: a phase II, randomized, controlled study. Vaccine. 2014 Mar 26;32(15):1745-53.http://www.ncbi.nlm.nih.gov/pubmed/24508036?tool=bestpractice.com 因此,医生应尽量确保患者接种两剂疫苗。
Shingrix® 比 Zostavax® 引起的注射部位反应更多。接受第二剂后的 3 级全身性疫苗反应(定义为妨碍正常日常活动的症状)也比第一剂后的更频繁。[27]Lal H, Cunningham AL, Godeaux O, et al; ZOE-50 Study Group. Efficacy of an adjuvanted herpes zoster subunit vaccine in older adults. N Engl J Med. 2015 May 28;372(22):2087-96.http://www.nejm.org/doi/full/10.1056/NEJMoa1501184http://www.ncbi.nlm.nih.gov/pubmed/25916341?tool=bestpractice.com现已证实 Shingrix® 对先前接种过 Zostavax® 的患者是安全的,并且具有免疫原性。[30]Grupping K, Campora L, Douha M, et al. Immunogenicity and Safety of the HZ/su Adjuvanted Herpes Zoster Subunit Vaccine in Adults Previously Vaccinated With a Live Attenuated Herpes Zoster Vaccine. J Infect Dis. 2017 Dec 12;216(11):1343-1351.https://academic.oup.com/jid/article/216/11/1343/4209275http://www.ncbi.nlm.nih.gov/pubmed/2902912?tool=bestpractice.com 此外,它可与流感疫苗同时接种,而不干扰免疫应答或引起安全问题。[31]Schwarz TF, Aggarwal N, Moeckesch B, et al. Immunogenicity and safety of an adjuvanted herpes zoster subunit vaccine coadministered with seasonal influenza vaccine in adults aged 50 years or older. J Infect Dis. 2017 Dec 12;216(11):1352-1361.https://academic.oup.com/jid/article/216/11/1352/4191338http://www.ncbi.nlm.nih.gov/pubmed/29029224?tool=bestpractice.com
在 FDA 批准后,美国疾病预防控制中心免疫接种实践咨询委员会 (Advisory Committee on Immunization Practices, ACIP) 推荐使用 Shingrix® 代替 Zostavax® 来预防≥50 岁人群的带状疱疹和带状疱疹后遗神经痛。[32]Dooling KL, Guo A, Patel M, et al. Recommendations of the Advisory Committee on Immunization Practices for use of herpes zoster vaccines. MMWR Morb Mortal Wkly Rep. 2018 Jan 26;67(3):103-108.https://www.cdc.gov/mmwr/volumes/67/wr/mm6703a5.htm?s_cid=mm6703a5_whttp://www.ncbi.nlm.nih.gov/pubmed/29370152?tool=bestpractice.com这表示推荐的接种年龄从之前的≥60 岁有所降低。ACIP 还推荐所有先前接种过 Zostavax® 的患者至少在初次接种后的 2 个月之后接种 Shingrix®。需要注意的是,Zostavax® 是以单次剂量皮下注射;Shingrix® 为分 2 次(之间相隔 2 至 6 个月)肌内注射;注射方式的错误促使 CDC 制定了对医生的提醒。[33]Shimabukuro TT, Miller ER, Strikas RA, et al. Notes from the Field: vaccine administration errors involving recombinant zoster vaccine — United States, 2017–2018. MMWR Morb Mortal Wkly Rep 2018;67:585–586.https://www.cdc.gov/mmwr/volumes/67/wr/mm6720a4.htmhttp://www.ncbi.nlm.nih.gov/pubmed/29795075?tool=bestpractice.com
尽管在理论上来说,Shingrix® 对免疫力低下的患者是安全的,但 ACIP 尚未就此对该群体提出推荐。这些患者仍在等待制造商提供更多数据。
ACIP 推荐可将 Zostavax® 用于年龄≥60 岁的人群(但首选 Shingrix®)。[34]Kim DK, Riley LE, Hunter P. Advisory Committee on Immunization Practices recommended immunization schedule for adults aged 19 years or older - United States, 2018. MMWR Morb Mortal Wkly Rep. 2018 Feb 9;67(5):158-160.https://www.cdc.gov/mmwr/volumes/67/wr/mm6705e3.htm?s_cid=mm6705e3_whttp://www.ncbi.nlm.nih.gov/pubmed/29420462?tool=bestpractice.com Shingrix® 也在 2018 年 1 月获得了欧洲药品管理局 (European Medicines Agency) 人用药品委员会的上市许可。