乙型肝炎疫苗——从预防到治疗
DOI: 10.12449/JCH240524
利益冲突声明:本文不存在任何利益冲突。
作者贡献声明:刘义思负责文献检索和撰写;陈新月负责拟定写作思路,终审定稿。
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摘要: 乙型肝炎疫苗的接种是预防HBV感染最经济、有效的方法。分子生物学和基因工程的进步使得疫苗的制造工艺不断完善,乙型肝炎疫苗也从最开始的血源性疫苗逐渐发展至当下所应用的重组疫苗。预防性乙型肝炎疫苗在临床中已试用于HBsAg清除人群以提高抗-HBs水平,且具有安全性及有效性。并且作为治疗CHB新药的多种靶点之一,基于HBsAg的治疗性乙型肝炎疫苗已经在研发和临床试验中。Abstract: Hepatitis B vaccination is the most economical and effective way to prevent HBV infection. The advances in molecular biology and genetic engineering have continuously improved the manufacturing process of vaccines, and hepatitis B vaccine has gradually developed from the initial plasma-derived vaccine to the currently used recombinant vaccine. Preventive hepatitis B vaccine has been clinically tested in patients with HBsAg seroclearance to increase the level of anti-HBs, with certain safety and efficacy. As one of the multiple targets for new drugs in the treatment of chronic hepatitis B, a therapeutic hepatitis B vaccine based on HBsAg is already in the stages of research and development and clinical trial.
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Key words:
- Hepatitis B, Chronic /
- Hepatitis B Vaccines /
- Clinical Trial
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[1] SZMUNESS W, STEVENS CE, HARLEY EJ, et al. Hepatitis B vaccine: Demonstration of efficacy in a controlled clinical trial in a high-risk population in the United States[J]. N Engl J Med, 1980, 303( 15): 833- 841. DOI: 10.1056/NEJM198010093031501. [2] MAUPAS P, CHIRON JP, BARIN F, et al. Efficacy of hepatitis B vaccine in prevention of early HBsAg carrier state in children. Controlled trial in an endemic area(Senegal)[J]. Lancet, 1981, 1( 8215): 289- 292. DOI: 10.1016/s0140-6736(81)91908-5. [3] CUI FQ, SHEN LP, LI L, et al. Prevention of chronic hepatitis B after 3 decades of escalating vaccination policy, China[J]. Emerg Infect Dis, 2017, 23( 5): 765- 772. DOI: 10.3201/eid2305.161477. [4] BLUMBERG BS. A“new” antigen in leukemia sera[J]. JAMA, 1965, 191( 7): 541. DOI: 10.1001/jama.1965.03080070025007. [5] BLUMBERG BS. Australia antigen and the biology of hepatitis B[J]. Science, 1977, 197( 4298): 17- 25. DOI: 10.1126/science.325649. [6] PURCELL RH, GERIN JL. Hepatitis B vaccines. On the threshold[J]. Am J Clin Pathol, 1978, 70( 1 Suppl): 159- 169. [7] MARMION BP. Prospects for new viral vaccines[J]. Philos Trans R Soc Lond B Biol Sci, 1980, 290( 1040): 395- 407. DOI: 10.1098/rstb.1980.0103. [8] GALAMBOS L, SEWELL JE. Networks of innovation: vaccine development at Merck, Sharp& Dohme, and Mulford, 1895-1995[M]. Cambridge: Cambridge University Press, 1995. [9] MCMAHON BJ, HELMINIAK C, WAINWRIGHT RB, et al. Frequency of adverse reactions to hepatitis B vaccine in 43, 618 persons[J]. Am J Med, 1992, 92( 3): 254- 256. DOI: 10.1016/0002-9343(92)90073-k. [10] MAUPAS P, GOUDEAU A, COURSAGET P, et al. Immunisation against hepatitis B in man[J]. Lancet, 1976, 1( 7974): 1367- 1370. DOI: 10.1016/s0140-6736(76)93023-3. [11] SZMUNESS W, STEVENS CE, ZANG EA, et al. A controlled clinical trial of the efficacy of the hepatitis B vaccine(Heptavax B): A final report[J]. Hepatology, 1981, 1( 5): 377- 385. DOI: 10.1002/hep.1840010502. [12] SHAW FE Jr, GRAHAM DJ, GUESS HA, et al. Postmarketing surveillance for neurologic adverse events reported after hepatitis B vaccination. Experience of the first three years[J]. Am J Epidemiol, 1988, 127( 2): 337- 352. DOI: 10.1093/oxfordjournals.aje.a114808. [13] VENTERS C, GRAHAM W, CASSIDY W. Recombivax-HB: Perspectives past, present and future[J]. Expert Rev Vaccines, 2004, 3( 2): 119- 129. DOI: 10.1586/14760584.3.2.119. [14] van den ENDE C, MARANO C, van AHEE A, et al. The immunogenicity of GSK’s recombinant hepatitis B vaccine in children: A systematic review of 30 years of experience[J]. Expert Rev Vaccines, 2017, 16( 8): 789- 809. DOI: 10.1080/14760584.2017.1338569. [15] STEVENS CE. Yeast-recombinant hepatitis B vaccine. Efficacy with hepatitis B immune globulin in prevention of perinatal hepatitis B virus transmission[J]. JAMA, 1987, 257( 19): 2612- 2616. DOI: 10.1001/jama.257.19.2612. [16] BRUSS V, THOMSSEN R. Mapping a region of the large envelope protein required for hepatitis B virion maturation[J]. J Virol, 1994, 68( 3): 1643- 1650. DOI: 10.1128/JVI.68.3.1643-1650.1994. [17] BLANCHET M, SUREAU C. Infectivity determinants of the hepatitis B virus pre-S domain are confined to the N-terminal 75 amino acid residues[J]. J Virol, 2007, 81( 11): 5841- 5849. DOI: 10.1128/JVI.00096-07. [18] SHOUVAL D, ILAN Y, ADLER R, et al. Improved immunogenicity in mice of a mammalian cell-derived recombinant hepatitis B vaccine containing pre-S1 and pre-S2 antigens as compared with conventional yeast-derived vaccines[J]. Vaccine, 1994, 12( 15): 1453- 1459. DOI: 10.1016/0264-410x(94)90155-4. [19] SHOUVAL D, ROGGENDORF H, ROGGENDORF M. Enhanced immune response to hepatitis B vaccination through immunization with a Pre-S1/Pre-S2/S vaccine[J]. Med Microbiol Immunol, 2015, 204( 1): 57- 68. DOI: 10.1007/s00430-014-0374-x. [20] HO JKT, JEEVAN-RAJ B, NETTER HJ. Hepatitis B virus(HBV) subviral particles as protective vaccines and vaccine platforms[J]. Viruses, 2020, 12( 2): 126. DOI: 10.3390/v12020126. [21] Centers for Disease Control and Prevention(CDC). Progress in hepatitis B prevention through universal infant vaccination: China, 1997-2006[J]. MMWR Morb Mortal Wkly Rep, 2007, 56( 18): 441- 445. [22] WANG SN, SMITH H, PENG ZX, et al. Increasing coverage of hepatitis B vaccination in China: A systematic review of interventions and implementation experiences[J]. Medicine(Baltimore), 2016, 95( 19): e3693. DOI: 10.1097/MD.0000000000003693. [23] CAO XZ, YI W, WANG FC, et al. Mother-to-child blockade with telbivudine of pregnant women infected with hepatitis B virus and the influence on the immune response to hepatitis B vaccine of infants[J/CD]. Chin J Exp Clin Infect Dis(Electronic Edition), 2022, 16( 3): 158- 164. DOI: 10.3877/cma.j.issn.1674-1358.2022.03.003.曹秀贞, 易为, 王夫川, 等. 乙型肝炎病毒感染孕妇替比夫定母婴阻断及其对婴儿乙肝疫苗免疫应答的影响[J/CD]. 中华实验和临床感染病杂志(电子版), 2022, 16( 3): 158- 164. DOI: 10.3877/cma.j.issn.1674-1358.2022.03.003. [24] SUN ZT, MING LH, ZHU X, et al. Prevention and control of hepatitis B in China[J]. J Med Virol, 2002, 67( 3): 447- 450. DOI: 10.1002/jmv.10094. [25] CUI J, CAO L, ZHENG JS, et al. Reported coverage of vaccines in the National Immunization Program of China, 2015[J]. Chin J Vaccines Immun, 2017, 23( 6): 601- 607. DOI: 10.19914/j.cjvi.2017.06.001.崔健, 曹雷, 郑景山, 等. 中国2015年国家免疫规划疫苗报告接种率分析[J]. 中国疫苗和免疫, 2017, 23( 6): 601- 607. DOI: 10.19914/j.cjvi.2017.06.001. [26] YIN XR, HAN GR, ZHANG H, et al. A real-world prospective study of mother-to-child transmission of HBV in China using a mobile health application(shield 01)[J]. J Clin Transl Hepatol, 2020, 8( 1): 1- 8. DOI: 10.14218/JCTH.2019.00057. [27] COUILLIN I, POL S, MANCINI M, et al. Specific vaccine therapy in chronic hepatitis B: Induction of T cell proliferative responses specific for envelope antigens[J]. J Infect Dis, 1999, 180( 1): 15- 26. DOI: 10.1086/314828. [28] POL S, NALPAS B, DRISS F, et al. Efficacy and limitations of a specific immunotherapy in chronic hepatitis B[J]. J Hepatol, 2001, 34( 6): 917- 921. DOI: 10.1016/s0168-8278(01)00028-9. [29] DIKICI B, KALAYCI AG, OZGENC F, et al. Therapeutic vaccination in the immunotolerant phase of children with chronic hepatitis B infection[J]. Pediatr Infect Dis J, 2003, 22( 4): 345- 349. DOI: 10.1097/01.inf.0000059443.49414.8b. [30] HOA PT, HUY NT, THU LT, et al. Randomized controlled study investigating viral suppression and serological response following pre-S1/pre-S2/S vaccine therapy combined with lamivudine treatment in HBeAg-positive patients with chronic hepatitis B[J]. Antimicrob Agents Chemother, 2009, 53( 12): 5134- 5140. DOI: 10.1128/AAC.00276-09. [31] OLIVIERO B, CERINO A, VARCHETTA S, et al. Enhanced B-cell differentiation and reduced proliferative capacity in chronic hepatitis C and chronic hepatitis B virus infections[J]. J Hepatol, 2011, 55( 1): 53- 60. DOI: 10.1016/j.jhep.2010.10.016. [32] XU XS, SHANG QH, CHEN XY, et al. Reversal of B-cell hyperactivation and functional impairment is associated with HBsAg seroconversion in chronic hepatitis B patients[J]. Cell Mol Immunol, 2015, 12( 3): 309- 316. DOI: 10.1038/cmi.2015.25. [33] SALIMZADEH L, LE BERT N, DUTERTRE CA, et al. PD-1 blockade partially recovers dysfunctional virus-specific B cells in chronic hepatitis B infection[J]. J Clin Invest, 2018, 128( 10): 4573- 4587. DOI: 10.1172/JCI121957. [34] NEUMANN-HAEFELIN C, THIMME R. Entering the spotlight: Hepatitis B surface antigen-specific B cells[J]. J Clin Invest, 2018, 128( 10): 4257- 4259. DOI: 10.1172/JCI124098. [35] BURTON AR, PALLETT LJ, MCCOY LE, et al. Circulating and intrahepatic antiviral B cells are defective in hepatitis B[J]. J Clin Invest, 2018, 128( 10): 4588- 4603. DOI: 10.1172/JCI121960. [36] WU ZQ, TAN L, GAN WQ, et al. The relationship between the clearance of HBsAg and the remodeling of B cell subsets in CHB patients treated with Peg-IFN-Α[J]. Ann Transl Med, 2021, 9( 5): 414. DOI: 10.21037/atm-21-409. [37] MOUCARI R, KOREVAAR A, LADA O, et al. High rates of HBsAg seroconversion in HBeAg-positive chronic hepatitis B patients responding to interferon: A long-term follow-up study[J]. J Hepatol, 2009, 50( 6): 1084- 1092. DOI: 10.1016/j.jhep.2009.01.016. [38] KIM GA, LIM YS, AN J, et al. HBsAg seroclearance after nucleoside analogue therapy in patients with chronic hepatitis B: Clinical outcomes and durability[J]. Gut, 2014, 63( 8): 1325- 1332. DOI: 10.1136/gutjnl-2013-305517. [39] LI H, XU WT, DENG BC, et al. Research progress on functional cure of chronic hepatitis B by nucleoside(acid) analogues combined with pegylated interferon[J]. Clin J Med Off, 2022, 50( 9): 890- 893. DOI: 10.16680/j.1671-3826.2022.09.04.李卉, 许文涛, 邓宝成, 等. 核苷(酸)类似物联合聚乙二醇干扰素功能性治愈慢性乙型肝炎研究进展[J]. 临床军医杂志, 2022, 50( 9): 890- 893. DOI: 10.16680/j.1671-3826.2022.09.04. [40] TERRAULT NA, LOK ASF, MCMAHON BJ, et al. Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance[J]. Hepatology, 2018, 67( 4): 1560- 1599. DOI: 10.1002/hep.29800. [41] European Association for the Study of the Liver. EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection[J]. J Hepatol, 2017, 67( 2): 370- 398. DOI: 10.1016/j.jhep.2017.03.021. [42] Chinese Society of Infectious Diseases, Chinese Medical Association; Chinese Society of Hepatology, Chinese Medical Association. Guidelines for the prevention and treatment of chronic hepatitis B(version 2019)[J]. J Clin Hepatol, 2019, 35( 12): 2648- 2669. DOI: 10.3969/j.issn.1001-5256.2019.12.007.中华医学会感染病学分会, 中华医学会肝病学分会. 慢性乙型肝炎防治指南(2019年版)[J]. 临床肝胆病杂志, 2019, 35( 12): 2648- 2669. DOI: 10.3969/j.issn.1001-5256.2019.12.007. [43] Chinese Society of Infectious Diseases, Chinese Medical Association; Chinese Society of Hepatology, Chinese Medical Association. The expert consensus on clinical cure(functional cure) of chronic hepatitis B[J]. Chin J Hepatol, 2019, 27( 8): 594- 603. DOI: 10.3969/j.issn.1001-5256.2019.08.008.中华医学会感染病学分会, 中华医学会肝病学分会. 慢性乙型肝炎临床治愈(功能性治愈)专家共识[J]. 临床肝胆病杂志, 2019, 35( 8): 1693- 1701. DOI: 10.3969/j.issn.1001-5256.2019.08.008. [44] LI MH, SUN FF, BI XY, et al. Consolidation treatment needed for sustained HBsAg-negative response induced by interferon-alpha in HBeAg positive chronic hepatitis B patients[J]. Virol Sin, 2022, 37( 3): 390- 397. DOI: 10.1016/j.virs.2022.03.001. [45] JIANG SW, CAI MH, ZHANG ZL, et al. The potential effect of HBV vaccination on off-treatment HBsAg reversion after interferon-induced HBsAg clearance[J]. Hum Vaccin Immunother, 2023, 19( 1): 2161254. DOI: 10.1080/21645515.2022.2161254. [46] SONG AX, WANG XX, LU JF, et al. Durability of hepatitis B surface antigen seroclearance and subsequent risk for hepatocellular carcinoma: A meta-analysis[J]. J Viral Hepat, 2021, 28( 4): 601- 612. DOI: 10.1111/jvh.13471. [47] LI MH, YI W, ZHANG L, et al. Predictors of sustained functional cure in hepatitis B envelope antigen-negative patients achieving hepatitis B surface antigen seroclearance with interferon-alpha-based therapy[J]. J Viral Hepat, 2019, 26( Suppl 1): 32- 41. DOI: 10.1111/jvh.13151. [48] WU YL, LIU YL, LU JF, et al. Durability of interferon-induced hepatitis B surface antigen seroclearance[J]. Clin Gastroenterol Hepatol, 2020, 18( 2): 514- 516. e 2. DOI: 10.1016/j.cgh.2019.04.020. [49] ZENG QL, YU ZJ, SHANG J, et al. Short-term peginterferon-induced high functional cure rate in inactive chronic hepatitis B virus carriers with low surface antigen levels[J]. Open Forum Infect Dis, 2020, 7( 6): ofaa208. DOI: 10.1093/ofid/ofaa208. [50] WU FP, WANG YK, CUI DD, et al. Short-term peg-IFN α-2b re-treatment induced a high functional cure rate in patients with HBsAg recurrence after stopping peg-IFN α-based regimens[J]. J Clin Med, 2023, 12( 1): 361. DOI: 10.3390/jcm12010361. [51] LIU YS, REN S, MA LN, et al. Clinical study of hepatitis B vaccine in achieving hepatitis B surface antibody seroconversion in patients with functional cure[J]. Braz J Infect Dis, 2023, 27( 6): 103703. DOI: 10.1016/j.bjid.2023.103703. [52] MANCINI-BOURGINE M, FONTAINE H, SCOTT-ALGARA D, et al. Induction or expansion of T-cell responses by a hepatitis B DNA vaccine administered to chronic HBV carriers[J]. Hepatology, 2004, 40( 4): 874- 882. DOI: 10.1002/hep.1840400417. [53] MA HY, LIM TH, LEERAPUN A, et al. Therapeutic vaccine BRII-179 restores HBV-specific immune responses in patients with chronic HBV in a phase Ib/IIa study[J]. JHEP Rep, 2021, 3( 6): 100361. DOI: 10.1016/j.jhepr.2021.100361. [54] Biosciences Brii. Brii bio presents new data highlighting progress towards achieving HBV functional cure at AASLD’s the liver meeting® 2023[EB/OL].( 2023-11-14)[ 2024-12-14]. https://www.briibio.com/en/media/press-release/20231114/. https://www.briibio.com/en/media/press-release/20231114/ [55] LOK AS, PAN CQ, HAN SH B, et al. Randomized phase II study of GS-4774 as a therapeutic vaccine in virally suppressed patients with chronic hepatitis B[J]. J Hepatol, 2016, 65( 3): 509- 516. DOI: 10.1016/j.jhep.2016.05.016. [56] GANE E, VERDON DJ, BROOKS AE, et al. Anti-PD-1 blockade with nivolumab with and without therapeutic vaccination for virally suppressed chronic hepatitis B: A pilot study[J]. J Hepatol, 2019, 71( 5): 900- 907. DOI: 10.1016/j.jhep.2019.06.028. [57] EVANS T, BUSSEY L, TEO S, et al. Phase 1b/2a study of heterologous ChAdOx1-HBV/MVA-HBV therapeutic vaccination(VTP-300) as monotherapy and combined with low-dose nivolumab in virally-suppressed patients with CHB on nucleos(t) ide analogues[J]. J Hepatol, 2022, 7( 77): S868. DOI: 10.1016/S0168-8278(22)02030-X. [58] YARDENI D, GHANY MG. Review article: Hepatitis B-current and emerging therapies[J]. Aliment Pharmacol Ther, 2022, 55( 7): 805- 819. DOI: 10.1111/apt.16828.
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