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50岁及年龄更大成人接种重组流感疫苗的效果研究
Efficacy of Recombinant Influenza Vaccine in Adults 50 Years of Age or Older


Lisa M. Dunkle ... 呼吸系统疾病 • 2017.06.22
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摘要


背景

我们需要改进流感疫苗以控制季节性流感疫情。2014~2015年以A/H3N2病毒为主导的流感季,疫苗与流感病毒株之间的抗原不匹配导致了许多疫苗的有效性降低。本试验对比了四价重组流感疫苗(RIV4)与标准剂量、鸡胚生产来源的四价灭活流感疫苗(IIV4)在该次流感期间流感季对老年人的保护作用。

 

方法

我们进行了一项随机、双盲、多中心的临床试验,在50岁及年龄更大人群中对比了RIV4(每株45 μg重组血凝素[HA],单次剂量180 μg蛋白质)和标准剂量IIV4(每株15 μg的HA,单次剂量60 μg蛋白质)对接种疫苗后14天或之后发生的、经由逆转录酶聚合酶链反应(RT-PCR)证实的流感样疾病的相对效果。该“流感样疾病”由试验方案事先定义,包含任意流感病毒株所致的流感样疾病。我们采集了有流感样疾病症状的参与者的鼻咽拭子,通过RT-PCR测定和培养来证实流感感染的诊断。主要终点设定为接种疫苗后14天或之后直至流感季结束这段时间内发生的、经由RT-PCR证实、符合试验方案定义的流感样疾病。

 

结果

共有9,003名参与者纳入研究并经随机分组;8,855例(98.4%)接受了试验疫苗接种并进行了预防效果的随访(即改良意向性治疗人群),8,604例(95.6%)完成了符合方案的随访(即改良符合方案人群)。在接种RIV4者中,经RT-PCR证实的流感感染率在改良符合方案人群中为2.2%(4,303人中96例),在改良意向性治疗人群中为2.2%(4,427人中96例)。在接种IIV4者中,流感感染率在改良符合方案人群中为3.2%(4,301人中138例),在改良意向性治疗人群中为3.1%(4,428人中138例)。共检测到甲型H3N2流感感染181例,乙型流感感染47例,以及未能分亚型的甲型流感感染6例。RIV4与IIV4相比感染流感样疾病的概率降低30%(95%置信区间[CI]为10%~47%;P=0.006),并且满足预设的主要非劣效性分析标准,以及RIV4优于IIV4的探索性优效性分析标准。两种疫苗的安全性相似。

 

结论

就经证实的流感样疾病而言,RIV4能提供给老年人比标准剂量IIV4更好的保护(由Protein Sciences资助;在ClinicalTrials.gov number注册号为NCT02285998)。





作者信息

Lisa M. Dunkle, M.D., Ruvim Izikson, M.D., M.P.H., Peter Patriarca, M.D., Karen L. Goldenthal, M.D., Derek Muse, M.D., Janice Callahan, Ph.D., and Manon M.J. Cox, Ph.D., for the PSC12 Study Team*
From Protein Sciences, Meriden, CT (L.M.D., R.I., M.M.J.C.); Biologics Consulting, Rockville, MD (P.P.); independent consultant, San Antonio, TX (K.L.G.); Jean Brown Research, Salt Lake City (D.M.); and Callahan Associates, San Diego, CA (J.C.).Address reprint requests to Dr. Dunkle at Protein Sciences, 1000 Research Pkwy., Meriden, CT 06450, or at ldunkle@proteinsciences.com. *A complete list of the members of the PSC12 Study Team is provided in the Supplementary Appendix, available at NEJM.org.

 

参考文献

1. Cox MMJ, Hashimoto Y. A fast track influenza virus vaccine produced in insect cells. J Invertebr Pathol 2011;107:Suppl:S31-S41

2. Katz JM, Webster RG. Efficacy of inactivated influenza A virus (H3N2) vaccines grown in mammalian cells or embryonated eggs. J Infect Dis 1989;160:191-198

3. Wang ML, Katz JM, Webster RG. Extensive heterogeneity in the hemagglutinin of egg-grown influenza viruses from different patients. Virology 1989;171:275-279

4. Rajakumar A, Swierkosz EM, Schulze IT. Sequence of an influenza virus hemagglutinin determined directly from a clinical sample. Proc Natl Acad Sci U S A 1990;87:4154-4158

5. Skowronski DM, Janjua NZ, De Serres G, et al. Low 2012-13 influenza vaccine effectiveness associated with mutation in the egg-adapted H3N2 vaccine strain not antigenic drift in circulating viruses. PLoS One 2014;9:e92153-e92153

6. Johansson BE, Cox MMJ. Influenza viral neuraminidase: the forgotten antigen. Expert Rev Vaccines 2011;10:1683-1695

7. Johansson BE, Matthews JT, Kilbourne ED. Supplementation of conventional influenza A vaccine with purified viral neuraminidase results in a balanced and broadened immune response. Vaccine 1998;16:1009-1015

8. Milián E, Kamen AA. Current and emerging cell culture manufacturing technologies for influenza vaccines. Biomed Res Int 2015;2015:504831-504831

9. Appiah GD, Blanton L, D’Mello T, et al. Influenza activity — United States, 2014–15 season and composition of the 2015–16 influenza vaccine. MMWR Morb Mortal Wkly Rep 2015;64:583-590

10. Flannery B, Clippard J. End-of-season influenza vaccine effectiveness estimates for the 2014-15 season: US Influenza Vaccine Effectiveness (Flu VE) Network. Atlanta: Advisory Committee on Immunization Practices, June 24, 2015.

11. Guidance for industry: e6 good clinical practices; consolidated guidance. Silver Spring, MD: Food and Drug Administration, 1996 (https://www.fda.gov/ucm/groups/fdagov-public/@fdagov-drugs-gen/documents/document/ucm073122.pdf).

12. Davidoff F, DeAngelis CD, Drazen JM, et al. Sponsorship, authorship, and accountability. N Engl J Med 2001;345:825-827

13. Gerdil C. The annual production cycle for influenza vaccine. Vaccine 2003;21:1776-1779

14. National and regional level outpatient and virus surveillance: FluView. Atlanta: Centers for Disease Control and Prevention, 2015 (http://gis.cdc.gov/grasp/fluview/fluportaldashboard.html); Season: 2014–15; Viral Surveillance: N/A.

15. PASS 13 statistical software. Salt Lake City: NCSS, 2014.

16. Keitel WA, Treanor JJ, El Sahly HM, et al. Comparative immunogenicity of recombinant influenza hemagglutinin (rHA) and trivalent inactivated vaccine (TIV) among persons > or =65 years old. Vaccine 2009;28:379-385

17. Flannery B, Thaker SN, Clippard J, et al. Interim estimates of 2013–14 seasonal influenza vaccine effectiveness — United States, February 2014. MMWR Morb Mortal Wkly Rep 2014;63:137-142

18. DiazGranados CA, Dunning AJ, Kimmel M, et al. Efficacy of high-dose versus standard-dose influenza vaccine in older adults. N Engl J Med 2014;371:635-645

19. Farrington CP, Manning G. Test statistics and sample size formulae for comparative binomial trials with null hypothesis of non-zero risk difference or non-unity relative risk. Stat Med 1990;9:1447-1454

20. Wang R, Lagakos SW, Ware JH, Hunter DJ, Drazen JM. Statistics in medicine — reporting of subgroup analyses in clinical trials. N Engl J Med 2007;357:2189-2194

21. Dunn OJ. Multiple comparisons among means. J Am Stat Assoc 1961;56:52-64

22. Estimates of deaths associated with seasonal influenza — United States, 1976–2007. MMWR Morb Mortal Wkly Rep 2010;59:1057-1062

23. Simonsen L, Clarke MJ, Williamson GD, Stroup DF, Arden NH, Schonberger LB. The impact of influenza epidemics on mortality: introducing a severity index. Am J Public Health 1997;87:1944-1950

24. Treanor JJ, El Sahly HM. Protective efficacy of a trivalent recombinant hemagglutinin protein vaccine (FluBlok) against culture-confirmed influenza in healthy adults: a randomized, placebo-controlled trial. Vaccine 2011;29:7733-7739

25. Cox MMJ, Karl Anderson D. Production of a novel influenza vaccine using insect cells: protection against drifted strains. Influenza Other Respir Viruses 2007;1:35-40

26. Baxter R, Patriarca PA, Ensor K, Izikson R, Goldenthal KL, Cox MM. Evaluation of the safety, reactogenicity and immunogenicity of FluBlok trivalent recombinant baculovirus-expressed hemagglutinin influenza vaccine administered intramuscularly to healthy adults 50-64 years of age. Vaccine 2011;29:2272-2278

27. Safdar A, Rodriguez MA, Fayad LE, et al. Dose-related safety and immunogenicity of baculovirus-expressed trivalent influenza vaccine: a double-blind, controlled trial in adult patients with non-Hodgkin B cell lymphoma. J Infect Dis 2006;194:1394-1397

28. Powers DC, Smith GE, Anderson EL, et al. Influenza A virus vaccines containing purified recombinant H3 hemagglutinin are well tolerated and induce protective immune responses in healthy adults. J Infect Dis 1995;171:1595-1599

29. Treanor JJ, Schiff GM, Hayden FG, et al. Safety and immunogenicity of a baculovirus-expressed hemagglutinin influenza vaccine: a randomized controlled trial. JAMA 2007;297:1577-1582

30. Nachbagauer R, Choi A, Izikson R, Cox MM, Palese P, Krammer F. Age dependence and isotype specificity of influenza virus hemagglutinin stalk-reactive antibodies in humans. MBio 2016;7:e01996-15

31. Monto AS, Petrie JG, Cross RT, et al. Antibody to influenza virus neuraminidase: an independent correlate of protection. J Infect Dis 2015;212:1191-1199

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