Using serological surrogate indicators to evaluate pneumococcal conjugate vaccine efficacy: supporting new vaccine development
-
摘要: 基于肺炎球菌性疾病在全球范围内具有较高疾病负担的现实,世界卫生组织(WHO)推荐所有国家考虑将肺炎球菌结合疫苗(PCV)纳入本国的免疫规划。然而,由于肺炎球菌性疾病发病率低,病原学诊断和监测难度大,开展疫苗针对疾病的保护效果评估存在诸多困难。如能确定疫苗保护效力的替代指标,将极大地提升新疫苗研发的效率。基于已经上市的7价肺炎球菌结合疫苗(PCV7)临床试验过程中获得的疫苗针对疾病的保护效果和血清学效力的数据,WHO建立了PCV预防侵袭性肺炎球菌疾病(IPD)的抗体保护性阈值,建议将基于酶联免疫吸附试验(ELISA)方法检测的IgG水平达到0.35 μg/mL作为PCV接种后预防IPD的保护性水平,并在新PCV疫苗注册审批时,应用该阈值来评估疫苗针对IPD的保护效果。但该替代指标不能用于评估针对非侵袭性肺炎球菌疾病的保护效果,同时该阈值只适用于人群水平,不能保证在个体水平为预防IPD提供完全保护。
-
关键词:
- 肺炎球菌结合疫苗(PCV) /
- 疫苗保护效力 /
- 血清学指标
Abstract: Considering high disease burden of pneumococcal disease globally, World Health Organization (WHO) recommends pneumococcal conjugate vaccine (PCV) should be included into national immunization program in all countries. However, the difficulty in evaluating vaccine effectiveness for pneumococcal diseases slows down the new vaccine development due to low incidence of the disease and hard to diagnosis and surveillance. A surrogate indicator for vaccine efficacy will improve the vaccine research and development effectively. The serological efficacy data and vaccine effectiveness data from clinical trials for 7-valent pneumococcal conjugate vaccine (PCV7) was used by WHO to establish an antibody protective threshold against invasive pneumococcal diseases (IPD). WHO suggests that a 0.35 μg/ml immunoglobulin G (IgG) level tested by enzyme-linked immunosorbent assay (ELISA) could be considered as a protective level for PCV preventing IPD, and using this threshold to estimate the vaccine effectiveness against IPD when evaluating a new PCV for its licensure. However, this surrogate indicator should not be used for evaluating vaccine effectiveness for non-invasive pneumococcal diseases. Also, the threshold should be considered at population level and it does not indicate to prevent every IPD at individual level. -
[1] World Health Organization. Pneumococcal vaccines WHO position paper – 2012[J]. Wkly Epidemiol Rec, 2012, 87(14): 129 – 144. [2] Black S, Shinefield H, Fireman B, et al. Efficacy, safety and immunogenicity of heptavalent pneumococcal conjugate vaccine in children. Northern California Kaiser Permanente Vaccine Study Center Group[J]. Pediatr Infect Dis J, 2000, 19(3): 187 – 195. doi: 10.1097/00006454-200003000-00003 [3] Advisory Committee on Immunization Practices. Preventing pneumococcal disease among infants and young children. Recommendations of the Advisory Committee on Immunization Practices (ACIP)[J]. Morbidity and Mortality Weekly Report Recommendations and Reports, 2000, 49(RR – 9): 1. [4] Siber GR, Chang I, Baker S, et al. Estimating the protective concentration of anti-pneumococcal capsular polysaccharide antibodies[J]. Vaccine, 2007, 25(19): 3816 – 3826. doi: 10.1016/j.vaccine.2007.01.119 [5] World Health Organization. Recommendations to assure the quality, safety and efficacy of pneumococcal conjugate vaccines[EB/OL]. [2015 – 08 – 01]. http://www.who.int/biologicals/areas/vaccines/pneumo/Pneumo_final_23APRIL_2010.pdf?ua=1. [6] Geno KA, Gilbert GL, Song JY, et al. Pneumococcal capsules and their types: past, present, and future[J]. Clinical Microbiology Reviews, 2015, 28(3): 871 – 899. doi: 10.1128/CMR.00024-15 [7] Klugman KP, Black S, Dagan R, et al. Pneumococcal conjugate vaccine and pneumococcal common protein vaccines[M]//Plotkin SA, Mortimer EA. Vaccine. 6th Edition. Philadelphia: W. B. Saunders Co, 2013: 504 – 541. [8] Jódar L, Butler J, Carlone G, et al. Serological criteria for evaluation and licensure of new pneumococcal conjugate vaccine formulations for use in infants[J]. Vaccine, 2003, 21(23): 3265 – 3272. doi: 10.1016/S0264-410X(03)00230-5 [9] Klugman KP, Madhi SA, Huebner RE, et al. A trial of a 9-valent pneumococcal conjugate vaccine in children with and those without HIV infection[J]. New England Journal of Medicine, 2003, 349(14): 1341 – 1348. doi: 10.1056/NEJMoa035060 [10] O'Brien KL, Moulton LH, Reid R, et al. Efficacy and safety of seven-valent conjugate pneumococcal vaccine in American Indian children: group randomized trial[J]. The Lancet, 2003, 362(9381): 355 – 361. doi: 10.1016/S0140-6736(03)14022-6 [11] Schuerman L, Prymula R, Henckaerts I, et al. ELISA IgG concentrations and opsonophagocytic activity following pneum-ococcal protein D conjugate vaccination and relationship to efficacy against acute otitis media[J]. Vaccine, 2007, 25(11): 1962 – 1968. doi: 10.1016/j.vaccine.2006.12.008 [12] Kelly DF, Pollard AJ, Moxon ER. Immunological memory: the role of B cells in long-term protection against invasive bacterial pathogens[J]. JAMA, 2005, 294(23): 3019 – 3023. doi: 10.1001/jama.294.23.3019 [13] Goldblatt D, Richmond PE, Thornton C, et al. The induction of immunologic memory after vaccination with Haemophilus influenzae type b conjugate and acellular pertussis-containing diphtheria, tetanus, and pertussis vaccine combination[J]. Journal of Infectious Diseases, 1999, 180(2): 538 – 541. doi: 10.1086/jid.1999.180.issue-2 [14] Goldblatt D, Ramakrishnan M, O'Brien K. Using the impact of pneumococcal vaccines on nasopharyngeal carriage to aid licensing and vaccine implementation; a PneumoCarr meeting report March 27 – 28, 2012, Geneva[J]. Vaccine, 2013, 32(1): 146 – 152. doi: 10.1016/j.vaccine.2013.06.040 [15] Principi N, Esposito S. Serological criteria and carriage measurement for evaluation of new pneumococcal vaccines[J]. Human Vaccines, 2015, 11(6): 1494 – 1500. doi: 10.1080/21645515.2015.1033600 [16] Andrews NJ, Waight PA, Burbidge P, et al. Serotype-specific effectiveness and correlates of protection for the 13-valent pneumococcal conjugate vaccine: a post licensure indirect cohort study[J]. Lancet Infectious Diseases, 2014, 14(9): 839 – 846. doi: 10.1016/S1473-3099(14)70822-9 [17] Centers for Disease Control and Prevention (CDC). Licensure of a 13-valent pneumococcal conjugate vaccine (PCV13) and recommendations for use among children –Advisory Committee on Immunization Practices (ACIP), 2010[J]. Morbidity and Mortality Weekly Report, 2010, 59(9): 258 – 261. [18] Kaplan SL, Barson WJ, Lin PL, et al. Early trends for invasive pneumococcal infections in children after the introduction of the 13-valent pneumococcal conjugate vaccine[J]. Pediatric Infectious Disease Journal, 2013, 32(3): 203 – 207. doi: 10.1097/INF.0b013e318275614b [19] Moore M, Link-Gelles R, Schaffner W, et al. Effect of use of 13-valent pneum-ococcal conjugate vaccine in children on invasive pneumococcal disease in children and adults in the USA: analysis of multisite, population-based surveillance[J]. Lancet Infect Dis, 2015, 15(3): 301 – 309. doi: 10.1016/S1473-3099(14)71081-3 [20] Miller E, Andrews NJ, Waight PA, et al. Effectiveness of the new serotypes in the 13-valent pneumococcal conjugate vaccine[J]. Vaccine, 2011, 29(49): 9127 – 9131. doi: 10.1016/j.vaccine.2011.09.112 [21] Waight P, Andrews N, Ladhani S. Effect of the 13-valent pneumococcal conjugate vaccine on invasive pneumococcal disease in England and Wales 4 years after its introduction: an observational cohort study[J]. Lancet Infect Dis, 2015, 15(5): 535 – 543. doi: 10.1016/S1473-3099(15)70044-7 [22] Picazo J, Ruiz-Contreras J, Casado-Flores J, et al. Impact of introduction of conjugate vaccines in the vaccination schedule on the incidence of pediatric invasive pneumococcal disease requiring hospitalization in Madrid 2007 to 2011[J]. Pediatric Infectious Disease Journal, 2013, 32(6): 656 – 661. doi: 10.1097/INF.0b013e31827e8594 [23] Harboe ZB, Dalby T, Weinberger DM, et al. Impact of 13-valent pneumococcal conjugate vaccination in invasive pneumococcal disease incidence and mortality[J]. Clin Infect Dis, 2014, 59(8): 1066 – 1073. doi: 10.1093/cid/ciu524 [24] Ben-Shimol S, Greenberg D, Givon-Lavi N, et al. Early impact of sequential introduction of 7-valent and 13-valent pneumococcal conjugate vaccine on IPD in Israeli children <5 years: an active prospective nationwide surveillance[J]. Vaccine, 2014, 32(27): 3452 – 3459. doi: 10.1016/j.vaccine.2014.03.065 [25] Simonsen L, Taylor RJ, Schuck-Paim C, et al. Effect of 13-valent pneumococcal conjugate vaccine on admissions to hospital 2 years after its introduction in the USA: a time series analysis[J]. Lancet Respir Med, 2014, 2(5): 387 – 394. doi: 10.1016/S2213-2600(14)70032-3 [26] Hortal M, Estevan M, Meny M, et al. Impact of pneumococcal conjugate vaccines on the incidence of pneumonia in hospitalized children after five years of its introduction in Uruguay[J]. PLoS One, 2014, 9(6): e98567. doi: 10.1371/journal.pone.0098567 [27] Pírez MC, Algorta G, Chamorro F, et al. Changes in hospitalizations for pneumonia after universal vaccination with pneumococcal conjugate vaccines 7/13 valent and Haemophilus influenzae type b conjugate vaccine in a Pediatric Referral Hospital in Uruguay[J]. Pediatric Infectious Disease Journal, 2014, 33(7): 753 – 759. doi: 10.1097/INF.0000000000000294 [28] Gentile Á, Bakir J, Bialorus L, et al. Impact of the 13-valent pneumococcal conjugate vaccine on the incidence of consolidated pneumonia in children younger than 5 years old in Pilar, Buenos Aires: a population-based study[J]. Arch Argent Pediatr, 2015, 113(6): 502 – 509. [29] Becker-Dreps S, Amaya E, Liu L, et al. Changes in childhood pneumonia and infant mortality rates following introduction of the 13-valent pneumococcal conjugate vaccine in Nicaragua[J]. Pediatric Infectious Disease Journal, 2014, 33(6): 637 – 642. doi: 10.1097/INF.0000000000000269 [30] Angoulvant F, Levy C, Grimprel E, et al. Early impact of 13-valent pneumococcal conjugate vaccine on community-acquired pneumonia in children[J]. Clinical Infectious Diseases, 2014, 58(7): 918 – 924. doi: 10.1093/cid/ciu006 [31] Berglund A, Ekelund M, Fletcher MA, et al. All-cause pneumonia hospitalizations in children <2 years old in Sweden, 1998 to 2012: impact of pneumococcal conjugate vaccine introduction[J]. PLoS One, 2014, 9(11): e112211. doi: 10.1371/journal.pone.0112211 [32] Greenberg D, Givon-Lavi N, Ben-Shimol S, et al. Impact of PCV7/PCV13 introduction on community-acquired alveolar pneumonia in children <5 years[J]. Vaccine, 2015, 33(36): 4623 – 4629. doi: 10.1016/j.vaccine.2015.06.062 [33] Zhao AS, Boyle S, Butrymowicz A. Impact of 13-valent pneumococcal conjugate vaccine on otitis media bacteriology[J]. International Journal of Pediatric Otorhinolaryngology, 2014, 78(3): 499 – 503. doi: 10.1016/j.ijporl.2013.12.028 [34] Kaplan SL, Center KJ, Barson WJ, et al. Multicenter surveillance of Streptococcus pneumoniae isolates from middle ear and mastoid cultures in the 13-valent pneumococcal conjugate vaccine era[J]. Clinical Infectious Diseases, 2015, 60(9): 1339 – 1345. [35] Ben-Shimol S, Givon-Lavi N, Leibovitz E, et al. Near-elimination of otitis media caused by 13-valent pneumococcal conjugate vaccine (PCV) serotypes in southern Israel shortly after sequential introduction of 7-valent/13-valent PCV[J]. Clinical Infectious Diseases, 2014, 59(12): 1724 – 1732. doi: 10.1093/cid/ciu683 [36] Lee GM, Kleinman K, Pelton SI, et al. Impact of 13-valent pneumococcal conjugate vaccination on Streptococcus pneumoniae carriage in young children in Massachusetts[J]. Journal of the Pediatric Infectious Diseases Society, 2014, 3(1): 23 – 32. doi: 10.1093/jpids/pit057 [37] Loughlin AM, Hsu K, Silverio AL, et al. Direct and indirect effects of PCV13 on nasopharyngeal carriage of PCV13 unique pneumococcal serotypes in Massachusetts' children[J]. Pediatric Infectious Disease Journal, 2014, 33(5): 504 – 510. doi: 10.1097/INF.0000000000000279 [38] Cohen R, Levy C, Bingen E, et al. Impact of 13-valent pneumococcal conjugate vaccine on pneumococcal nasopharyngeal carriage in children with acute otitis media[J]. Pediatric Infectious Disease Journal, 2012, 31(3): 297 – 301. doi: 10.1097/INF.0b013e318247ef84 [39] van Hoek AJ, Sheppard CL, Andrews NJ, et al. Pneumococcal carriage in children and adults two years after introduction of the thirteen valent pneumococcal conjugate vaccine in England[J]. Vaccine, 2014, 32(34): 4349 – 4355. doi: 10.1016/j.vaccine.2014.03.017 [40] Dagan R, Juergens C, Trammel J, et al. Efficacy of 13-valent pneumococcal conjugate vaccine (PCV13) versus that of 7-valent PCV (PCV7) against nasopharyngeal colonization of antibiotic-nonsusceptible Streptococcus pneumoniae[J]. J Infect Dis, 2015, 211(7): 1144 – 1153. doi: 10.1093/infdis/jiu576 [41] de Kluyver R. Enhanced invasive pneumococcal disease surveillance working group[J]. Commun Dis Intell Q Rep, 2013, 37(4): E448 – 452.
点击查看大图
计量
- 文章访问数: 1090
- HTML全文浏览量: 374
- PDF下载量: 107
- 被引次数: 0