B群流行性脑脊髓膜炎疫苗研究进展

赵伟; 白霜; 康艳丽; 吕敏; 王建; 李琴; 吴疆; 郑群

doi:10.11847/zgggws1137414

B群流行性脑脊髓膜炎疫苗研究进展

doi: 10.11847/zgggws1137414

赵伟¹,
白霜¹,
康艳丽¹,
吕敏¹,
王建¹,
李琴²,
吴疆^1, ,,
郑群^3, ,

1.
北京市疾病预防控制中心北京市预防医学研究中心免疫预防所，北京 100010
2.
首都医科大学燕京医学院
3.
首都医科大学基础医学院

详细信息

作者简介:
赵伟（1983 – ）男，陕西西安人，助理研究员，博士，研究方向：呼吸道疫苗评价工作

通讯作者:
吴疆，E-mail：wj81732@hotmail.com

郑群，E-mail：zhengqun00@aliyun.com

中图分类号: R 378.1 ⁺ 5；R 392-33
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- 被引次数: 0
出版历程
- 接收日期: 2021-11-11
- 网络出版日期: 2022-07-31
- 刊出日期: 2022-08-31

Development of group B meningococcal vaccine: a progress review

1.
Beijing Research Center for Preventive Medicine, Beijing Center for Disease Prevention and Control, Beijing 100013, China

摘要

摘要: 流行性脑脊髓膜炎（流脑）是由脑膜炎奈瑟菌感染引起的以脑脊髓膜炎和菌血症为主的呼吸道传染病，由于缺乏有效的预防手段，B血清群已经成为流脑主要的流行菌群之一。近年来，反向疫苗学技术的出现极大地推动了B群流脑疫苗的研究工作，疫苗的研制也取得了突破性进展，为研究出更为有效的流脑疫苗，本文对B群流脑疫苗领域中新型蛋白抗原疫苗、外膜囊泡疫苗和重组蛋白疫苗等方面的研究进展进行了综述。
- 流行性脑脊髓膜炎（流脑） /
- B血清群 /
- 疫苗 /
- 研究进展
Abstract: Epidemic cerebrospinal meningitis is a respiratory infectious disease caused by Neisseria meningitidis, most commonly manifesting as meningitis and septicaemia. Due to the lack of effective prevention measures, serogroup B Neisseria meningitidis (MenB) has become one of dominant epidemic bacterial groups. In recent years, the emergence of reverse vaccinology has greatly promoted the research on serogroup B meningococcal vaccine, and researches on the vaccine have also made a breakthrough. In order to develop a more effective meningococcal vaccine, this article reviews the research progress on new protein antigen vaccine, outer membrane vesicle vaccine and recombinant protein vaccine in the field of MenB vaccine.
- epidemic cerebrospinal meningitis /
- serogroup B meningococci /
- vaccine /
- research progress

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参考文献(56)

[1]	Rosenstein NE, Perkins BA, Stephens DS, et al. Meningococcal disease[J]. The New England Journal of Medicine, 2001, 344(18): 1378 – 1388. doi: 10.1056/NEJM200105033441807
[2]	Lingani C, Bergeron-Caron C, Stuart JM, et al. Meningococcal meningitis surveillance in the African meningitis belt, 2004 – 2013[J]. Clinical Infectious Diseases, 2015, 61(S5): S410 – S415.
[3]	Harrison LH. Epidemiological profile of meningococcal disease in the United States[J]. Clinical Infectious Diseases, 2010, 50(S2): S37 – S44. doi: 10.1086/648963
[4]	Granoff DM. Review of meningococcal group B vaccines[J]. Clinical Infectious Diseases, 2010, 50(S2): S54 – S65. doi: 10.1086/648966
[5]	Jafri RZ, Ali A, Messonnier NE, et al. Global epidemiology of invasive meningococcal disease[J]. Population Health Metrics, 2013, 11(1): 17. doi: 10.1186/1478-7954-11-17
[6]	夏昕, 湛志飞, 刘运芝, 等. 湖南省B群脑膜炎奈瑟菌药物敏感性及分型[J]. 中国公共卫生, 2011, 27(12): 1568 – 1569. doi: 10.11847/zgggws2011-27-12-28
[7]	徐颖华, 李亚南, 叶强. 中国脑膜炎球菌疫苗发展现状与挑战[J]. 中国公共卫生, 2021,doi: 10.11847/zgggws1136615.
[8]	Kelly DF, Rappuoli R. Reverse vaccinology and vaccines for serogroup B Neisseria meningitidis[M]//Pollard AJ, Finn A. Hot Topics in Infection and Immunity in Children II. Boston: Springer, 2005: 217 – 223.
[9]	Pizza M, Scarlato V, Masignani V, et al. Identification of vaccine candidates against serogroup B meningococcus by whole - genome sequencing[J]. Science, 2000, 287(5459): 1816 – 1820. doi: 10.1126/science.287.5459.1816
[10]	McNeil LK, Zagursky RJ, Lin SL, et al. Role of factor H binding protein in Neisseria meningitidis virulence and its potential as a vaccine candidate to broadly protect against meningococcal disease[J]. Microbiology and Molecular Biology Reviews, 2013, 77(2): 234 – 252. doi: 10.1128/MMBR.00056-12
[11]	Granoff DM, Ram S, Beernink PT. Does binding of complement factor H to the meningococcal vaccine antigen, factor H binding protein, decrease protective serum antibody responses?[J]. Clinical and Vaccine Immunology, 2013, 20(8): 1099 – 1107. doi: 10.1128/CVI.00260-13
[12]	Granoff DM, Giuntini S, Gowans FA, et al. Enhanced protective antibody to a mutant meningococcal factor H - binding protein with low - factor H binding[J]. JCI Insight, 2016, 1(14): e88907.
[13]	Beernink PT, Welsch JA, Bar-Lev M, et al. Fine antigenic specificity and cooperative bactericidal activity of monoclonal antibodies directed at the meningococcal vaccine candidate factor H - binding protein[J]. Infection and Immunity, 2008, 76(9): 4232 – 4240. doi: 10.1128/IAI.00367-08
[14]	Masignani V, Comanducci M, Giuliani MM, et al. Vaccination against Neisseria meningitidis using three variants of the lipoprotein GNA1870[J]. Journal of Experimental Medicine, 2003, 197(6): 789 – 799. doi: 10.1084/jem.20021911
[15]	Murphy E, Andrew L, Lee KL, et al. Sequence diversity of the factor H binding protein vaccine candidate in epidemiologically relevant strains of serogroup B Neisseria meningitidis[J]. The Journal of Infectious Diseases, 2009, 200(3): 379 – 389. doi: 10.1086/600141
[16]	Scarselli M, Aricò B, Brunelli B, et al. Rational design of a meningococcal antigen inducing broad protective immunity[J]. Science Translational Medicine, 2011, 3(91): 91ra62.
[17]	Beernink PT, Granoff DM. Bactericidal antibody responses induced by meningococcal recombinant chimeric factor H - binding protein vaccines[J]. Infection and Immunity, 2008, 76(6): 2568 – 2575. doi: 10.1128/IAI.00033-08
[18]	Granoff DM, Costa I, Konar M, et al. Binding of complement Factor H (FH) decreases protective anti - FH binding protein antibody responses of infant rhesus macaques immunized with a meningococcal Serogroup B vaccine[J]. The Journal of Infectious Diseases, 2015, 212(5): 784 – 792. doi: 10.1093/infdis/jiv081
[19]	Beernink PT, Giuntini S, Costa I, et al. Functional analysis of the human antibody response to meningococcal factor H binding protein[J]. mBio, 2015, 6(3): e00842.
[20]	Beernink PT, Shaughnessy J, Braga EM, et al. A meningococcal factor H binding protein mutant that eliminates factor H binding enhances protective antibody responses to vaccination[J]. The Journal of Immunology, 2011, 186(6): 3606 – 3614. doi: 10.4049/jimmunol.1003470
[21]	Lucidarme J, Tan L, Exley RM, et al. Characterization of Neisseria meningitidis isolates that do not express the virulence factor and vaccine antigen factor H binding protein[J]. Clinical and Vaccine Immunology, 2011, 18(6): 1002 – 1014. doi: 10.1128/CVI.00055-11
[22]	Giuntini S, Lujan E, Gibani MM, et al. Serum bactericidal antibody responses of adults immunized with the MenB-4C vaccine against genetically diverse serogroup B Meningococci[J]. Clinical and Vaccine Immunology, 2017, 24(1): e00430 – 16.
[23]	Tavano R, Capecchi B, Montanari P, et al. Mapping of the Neisseria meningitidis NadA cell - binding site: relevance of predicted α - helices in the NH₂ - terminal and dimeric coiled - coil regions[J]. Journal of Bacteriology, 2011, 193(1): 107 – 115. doi: 10.1128/JB.00430-10
[24]	Bambini S, De Chiara M, Muzzi A, et al. Neisseria adhesin A variation and revised nomenclature scheme[J]. Clinical and Vaccine Immunology, 2014, 21(7): 966 – 971. doi: 10.1128/CVI.00825-13
[25]	Wang X, Cohn A, Comanducci M, et al. Prevalence and genetic diversity of candidate vaccine antigens among invasive Neisseria meningitidis isolates in the United States[J]. Vaccine, 2011, 29(29/30): 4739 – 4744.
[26]	Liguori A, Malito E, Lo Surdo P, et al. Molecular basis of ligand - dependent regulation of NadR, the transcriptional repressor of meningococcal virulence factor NadA[J]. PLoS Pathogens, 2016, 12(4): e1005557. doi: 10.1371/journal.ppat.1005557
[27]	Vacca I, Del Tordello E, Gasperini G, et al. Neisserial heparin binding antigen (NHBA) contributes to the adhesion of Neisseria meningitidis to human epithelial cells[J]. PLoS One, 2016, 11(10): e0162878. doi: 10.1371/journal.pone.0162878
[28]	Ren XY, Eccles DA, Greig GA, et al. Genomic, transcriptomic, and phenotypic analyses of Neisseria meningitidis isolates from disease patients and their household contacts[J]. mSystems, 2017, 2(6): e00127 – 17.
[29]	Mulhall RM, Brehony C, O'Connor L, et al. Resolution of a protracted serogroup B meningococcal outbreak with whole - genome sequencing shows interspecies genetic transfer[J]. Journal of Clinical Microbiology, 2016, 54(12): 2891 – 2899. doi: 10.1128/JCM.00881-16
[30]	Serruto D, Spadafina T, Ciucchi L, et al. Neisseria meningitidis GNA2132, a heparin - binding protein that induces protective immunity in humans[J]. Proceedings of the National Academy of Sciences of the United States of America, 2010, 107(8): 3770 – 3775. doi: 10.1073/pnas.0915162107
[31]	Vu DM, Wong TT, Granoff DM. Cooperative serum bactericidal activity between human antibodies to meningococcal factor H binding protein and neisserial heparin binding antigen[J]. Vaccine, 2011, 29(10): 1968 – 1973. doi: 10.1016/j.vaccine.2010.12.075
[32]	Martin DR, Ruijne N, McCallum L, et al. The VR2 epitope on the PorA P1.7 – 2, 4 protein is the major target for the immune response elicited by the strain - specific group B meningococcal vaccine MeNZB[J]. Clinical and Vaccine Immunology, 2006, 13(4): 486 – 491. doi: 10.1128/CVI.13.4.486-491.2006
[33]	Oster P, Lennon D, O'Hallahan J, et al. MeNZB^TM: a safe and highly immunogenic tailor - made vaccine against the New Zealand Neisseria meningitidis serogroup B disease epidemic strain[J]. Vaccine, 2005, 23(17/18): 2191 – 2196.
[34]	Lewis S, Sadarangani M, Hoe JC, et al. Challenges and progress in the development of a serogroup B meningococcal vaccine[J]. Expert Review of Vaccines, 2009, 8(6): 729 – 745. doi: 10.1586/erv.09.30
[35]	Morley SL, Cole MJ, Ison CA, et al. Immunogenicity of a serogroup B meningococcal vaccine against multiple Neisseria meningitidis strains in infants[J]. The Pediatric Infectious Disease Journal, 2001, 20(11): 1054 – 1061. doi: 10.1097/00006454-200111000-00010
[36]	Holst J, Feiring B, Fuglesang JE, et al. Serum bactericidal activity correlates with the vaccine efficacy of outer membrane vesicle vaccines against Neisseria meningitidis serogroup B disease[J]. Vaccine, 2003, 21(7/8): 734 – 737.
[37]	Thornton V, Lennon D, Rasanathan K, et al. Safety and immuno-genicity of New Zealand strain meningococcal serogroup B OMV vaccine in healthy adults: beginning of epidemic control[J]. Vaccine, 2006, 24(9): 1395 – 1400. doi: 10.1016/j.vaccine.2005.09.043
[38]	Arnold R, Galloway Y, McNicholas A, et al. Effectiveness of a vaccination programme for an epidemic of meningococcal B in New Zealand[J]. Vaccine, 2011, 29(40): 7100 – 7106. doi: 10.1016/j.vaccine.2011.06.120
[39]	De Kleijn E, van Eijndhoven L, Vermont C, et al. Serum bactericidal activity and isotype distribution of antibodies in toddlers and schoolchildren after vaccination with RIVM hexavalent PorA vesicle vaccine[J]. Vaccine, 2001, 20(3/4): 352 – 358.
[40]	Tondella ML, Popovic T, Rosenstein NE, et al. Distribution of Neisseria meningitidis serogroup B serosubtypes and serotypes circulating in the United States. The Active Bacterial Core Surveillance Team[J]. Journal of Clinical Microbiology, 2000, 38(9): 3323 – 3328. doi: 10.1128/JCM.38.9.3323-3328.2000
[41]	Petousis-Harris H. Impact of meningococcal group B OMV vaccines, beyond their brief[J]. Human Vaccines and Immunothe-rapeutics, 2018, 14(5): 1058 – 1063. doi: 10.1080/21645515.2017.1381810
[42]	Fisseha M, Chen P, Brandt B, et al. Characterization of native outer membrane vesicles from lpxL mutant strains of Neisseria meningitidis for use in parenteral vaccination[J]. Infection and Immunity, 2005, 73(7): 4070 – 4080. doi: 10.1128/IAI.73.7.4070-4080.2005
[43]	Keiser PB, Biggs-Cicatelli S, Moran EE, et al. A phase 1 study of a meningococcal native outer membrane vesicle vaccine made from a group B strain with deleted lpxL1 and synX, over - expressed factor H binding protein, two PorAs and stabilized OpcA expression[J]. Vaccine, 2011, 29(7): 1413 – 1420. doi: 10.1016/j.vaccine.2010.12.039
[44]	Pajon R, Lujan E, Granoff DM. A meningococcal NOMV - FHbp vaccine for Africa elicits broader serum bactericidal antibody responses against serogroup B and non - B strains than a licensed serogroup B vaccine[J]. Vaccine, 2016, 34(5): 643 – 649. doi: 10.1016/j.vaccine.2015.12.034
[45]	Beernink PT, Vianzon V, Lewis LA, et al. A meningococcal outer membrane vesicle vaccine with overexpressed mutant FHbp elicits higher protective antibody responses in infant rhesus macaques than a licensed serogroup B vaccine[J]. mBio, 2019, 10(3): e01231 – 19.
[46]	Beernink PT, Ispasanie E, Lewis LA, et al. A meningococcal native outer membrane vesicle vaccine with attenuated endotoxin and overexpressed factor H binding protein elicits gonococcal bactericidal antibodies[J]. The Journal of Infectious Diseases, 2019, 219(7): 1130 – 1137. doi: 10.1093/infdis/jiy609
[47]	药品资讯网. FDA授予辉瑞疫苗rLP2086突破性疗法认定[J]. 临床合理用药杂志, 2014(14): 5.
[48]	Luo Y, Friese OV, Runnels HA, et al. The dual role of lipids of the lipoproteins in Trumenba, a self - adjuvanting vaccine against meningococcal meningitis B disease[J]. The AAPS Journal, 2016, 18(6): 1562 – 1575. doi: 10.1208/s12248-016-9979-x
[49]	Jiang HQ, Hoiseth SK, Harris SL, et al. Broad vaccine coverage predicted for a bivalent recombinant factor H binding protein based vaccine to prevent serogroup B meningococcal disease[J]. Vaccine, 2010, 28(37): 6086 – 6093. doi: 10.1016/j.vaccine.2010.06.083
[50]	Marshall HS, Richmond PC, Nissen MD, et al. A phase 2 open - label safety and immunogenicity study of a meningococcal B bivalent rLP2086 vaccine in healthy adults[J]. Vaccine, 2013, 31(12): 1569 – 1575. doi: 10.1016/j.vaccine.2013.01.021
[51]	Marshall HS, Richmond PC, Beeslaar J, et al. Meningococcal serogroup B - specific responses after vaccination with bivalent rLP2086: 4 year follow - up of a randomised, single - blind, placebo - controlled, phase 2 trial[J]. The Lancet Infectious Diseases, 2017, 17(1): 58 – 67. doi: 10.1016/S1473-3099(16)30314-0
[52]	Vesikari T, Østergaard L, Beeslaar J, et al. Persistence and 4 - year boosting of the bactericidal response elicited by two - and three - dose schedules of MenB - FHbp: a phase 3 extension study in adolescents[J]. Vaccine, 2019, 37(12): 1710 – 1719. doi: 10.1016/j.vaccine.2018.11.073
[53]	Ladhani SN, Andrews N, Parikh SR, et al. Vaccination of infants with meningococcal Group B Vaccine (4CMenB) in England[J]. The New England Journal of Medicine, 2020, 382(4): 309 – 317. doi: 10.1056/NEJMoa1901229
[54]	Vesikari T, Esposito S, Prymula R, et al. Immunogenicity and safety of an investigational multicomponent, recombinant, mening-ococcal serogroup B vaccine (4CMenB) administered concomi-tantly with routine infant and child vaccinations: results of two randomised trials[J]. The Lancet, 2013, 381(9869): 825 – 835. doi: 10.1016/S0140-6736(12)61961-8
[55]	Flacco ME, Manzoli L, Rosso A, et al. Immunogenicity and safety of the multicomponent meningococcal B vaccine (4CMenB) in children and adolescents: a systematic review and meta - analysis[J]. The Lancet Infectious Diseases, 2018, 18(4): 461 – 472. doi: 10.1016/S1473-3099(18)30048-3
[56]	Rodrigues CMC, Lucidarme J, Borrow R, et al. Genomic survei-llance of 4CMenB vaccine antigenic variants among disease - causing Neisseria meningitidis isolates, United Kingdom, 2010 – 2016[J]. Emerging Infectious Diseases, 2018, 24(4): 673 – 682. doi: 10.3201/eid2404.171480