Research progress of tuberculosis vaccine and vaccination strategy

doi:10.3969/j.issn.1000-6621.2021.06.018

Abstract

Abstract:

BCG vaccine is now the only approved and the most widely used tuberculosis vaccine worldwide. It can effectively prevent the tuberculous meningitis in infant and the disseminated tuberculosis, however, for teenagers and adults, as well as those who have been infected with MTB, the protection effect is poor. Therefore, the main research direction of tuberculosis prevention and control includes to develop new effective vaccines, to increase the immune intensity of vaccine and extend protection time of vaccines. The authors reviewed various tuberculosis vaccine types, inoculation routes and immunization strategies, and summarized the information of improving vaccine efficacy, in order to provide reference for the parallel improvement of pre-clinical and clinical trial protocols.

Key words: BCG vaccine, Vaccines, Vaccination, Review

WANG Yuan-zhi, LIANG Zheng-min, QU Meng-jin, ZHOU Xiang-mei. Research progress of tuberculosis vaccine and vaccination strategy[J]. Chinese Journal of Antituberculosis, 2021, 43(6): 625-630. doi: 10.3969/j.issn.1000-6621.2021.06.018

Figures/Tables 1

References 35

[1]	Peck M, Gacic-Dobo M, Diallo MS, et al. Global Routine Vaccination Coverage, 2018. MMWR Morb Mortal Wkly Rep, 2019,68(42):937-942. doi: 10.15585/mmwr.mm6842a1. doi: 10.15585/mmwr.mm6842a1 URL
[2]	World Health Organization. Summary of the WHO Position Paper on BCG vaccines: WHO position paper. Geneva:World Health Organization, 2018.
[3]	郭倩, 申晨, 申阿东. 干细胞与结核分枝杆菌交互作用的研究进展. 中国防痨杂志, 2021,43(2):186-189. doi: 10.3969/j.issn.1000-6621.2021.02.015. doi: 10.3969/j.issn.1000-6621.2021.02.015
[4]	World Health Organization. The global plan to end TB 2016-2020:the paradigm shift.Geneva:Stop TB Partnership, United Nations Office for Project Services, 2015.
[5]	陈柠, 孙琳, 申阿东, 等. 卡介苗接种后发生感染的可能原因研究现况. 中国防痨杂志, 2020,42(8):869-873. doi: 10.3969/j.issn.1000-6621.2020.08.017. doi: 10.3969/j.issn.1000-6621.2020.08.017
[6]	Nieuwenhuizen NE, Kulkarni PS, Shaligram U, et al. The recombinant Bacille Calmette-Guérin vaccine VPM1002:ready for clinical efficacy testing. Front Immunol, 2017,8:1147. doi: 10.3389/fimmu.2017.01147. doi: 10.3389/fimmu.2017.01147 pmid: 28974949
[7]	Gonzalo AJ, Marinova D, Martin C, et al. MTBVAC:attenuating the human pathogen of tuberculosis (TB) toward a promising vaccine against the TB epidemic. Front Immunol, 2017,8:1803. doi: 10.3389/fimmu.2017.01803. doi: 10.3389/fimmu.2017.01803 URL
[8]	Yang XY, Chen QF, Li YP, et al. Mycobacterium vaccae as adjuvant therapy to anti-tuberculosis chemotherapy in never treated tuberculosis patients: a meta-analysis. PLoS One, 2011,6(9):e23826. doi: 10.1371/journal.pone.0023826. doi: 10.1371/journal.pone.0023826 URL
[9]	Saqib M, Khatri R, Singh B, et al. Mycobacterium indicus pranii as a booster vaccine enhances BCG induced immunity and confers higher protection in animal models of tuberculosis. Tuberculosis (Edinb), 2016,101:164-173. doi: 10.1016/j.tube.2016.10.002. doi: S1472-9792(16)30239-6 pmid: 27865389
[10]	Munseri P, Said J, Amour M, et al. DAR-901 vaccine for the prevention of infection with Mycobacterium tuberculosis among BCG-immunized adolescents in Tanzania: A randomized controlled, double-blind phase 2b trial. Vaccine, 2020,38(46):7239-7245. doi: 10.1016/j.vaccine.2020.09.055. doi: 10.1016/j.vaccine.2020.09.055 URL
[11]	Vilaplana C, Montané E, Pinto S, et al. Double-blind, randomized, placebo-controlled phase I clinical trial of the therapeutical antituberculous vaccine RUTI. Vaccine, 2010,28(4):1106-1116. doi: 10.1016/j.vaccine.2009.09.134. doi: 10.1016/j.vaccine.2009.09.134 pmid: 19853680
[12]	Loxton AG, Knaul JK, Grode L, et al. Safety and immunogenicity of the recombinant Mycobacterium bovis BCG vaccine VPM1002 in HIV-unexposed newborn infants in South Africa. Clin Vaccine Immunol, 2017,24(2):e00439-16. doi: 10.1128/CVI.00439-16. doi: 10.1128/CVI.00439-16
[13]	Tameris M, Mearns H, Penn-Nicholson A, et al. Live-attenuated Mycobacterium tuberculosis vaccine MTBVAC versus BCG in adults and neonates: a randomised controlled, double-blind dose-escalation trial. Lancet Respir Med, 2019,7(9):757-770. doi: 10.1016/S2213-2600(19)30251-6. doi: 10.1016/S2213-2600(19)30251-6 URL
[14]	方刚, 顾小燕, 尹小芳. 母牛分枝杆菌菌苗辅助抗结核方案治疗肺结核对患者免疫功能及疾病转归的影响. 中国临床研究, 2020,33(4):501-504. doi: 10.13429/j.cnki.cjcr.2020.04.017. doi: 10.13429/j.cnki.cjcr.2020.04.017
[15]	Nell AS, D’Lom E, Bouic P, et al. Safety,tolerability,and immunogenicity of the novel antituberculous vaccine RUTI:randomized,placebocontrolled phase Ⅱ clinical trial in patients with latent tuberculosis infection. PLoS One, 2014,9:e89612. doi: 10.1371/journal.pone.0089612. doi: 10.1371/journal.pone.0089612 URL
[16]	Tait DR, Hatherill M, Van Der Meeren O, et al. Final Analysis of a Trial of M72/AS01 E Vaccine to Prevent Tuberculosis. N Engl J Med, 2019,381(25):2429-2439. doi: 10.1056/NEJMoa1909953. doi: 10.1056/NEJMoa1909953 URL
[17]	Coppola M, van Meijgaarden KE, Franken KL, et al. New genomewide algorithm identifies novel in-vivo expressed Mycobacterium tuberculosis antigens inducing human T-cell responses with classical and unconventional cytokine profiles. Sci Rep, 2016,6:37793. doi: 10.1038/srep37793. doi: 10.1038/srep37793 URL
[18]	李菲. 结核潜伏抗原筛选与治疗性融合蛋白疫苗的制备. 兰州: 兰州大学, 2016.
[19]	寇一鸣. 结核分枝杆菌新型疫苗的构建及免疫学评价. 长春: 吉林大学, 2018.
[20]	Darrah PA, Zeppa JJ, Maiello P, et al. Prevention of tuberculosis in macaques after intravenous BCG immunization. Nature, 2020,577(7788):95-102. doi: 10.1038/s41586-019-1817-8. doi: 10.1038/s41586-019-1817-8 URL
[21]	Fourie PB, Germishuizen WA, Wong YL, et al. Spray drying TB vaccines for pulmonary administration. Expert Opin Biol Ther, 2008,8(7):857-863. doi: 10.1517/14712598.8.7.857. doi: 10.1517/14712598.8.7.857 pmid: 18564902
[22]	Manjaly Thomas ZR, Satti I, Marshall JL, et al. Alternate aerosol and systemic immunisation with a recombinant viral vector for tuberculosis, MVA85A: a phase I randomised controlled trial. PLoS Med, 2019,16(4):e1002790. doi: 10.1371/journal.pmed.1002790. doi: 10.1371/journal.pmed.1002790 URL
[23]	Manjaly Thomas ZR, McShane H, Aerosol immunisation for TB: matching route of vaccination to route of infection. Trans R Soc Trop Med Hyg, 2015,109(3):175-181. doi: 10.1093/trstmh/tru206. doi: 10.1093/trstmh/tru206 URL
[24]	徐菀佚, 乔建斌, 马波, 等. 冻融-冻干法制备的流感疫苗脂质体的细胞免疫研究. 中国药科大学学报, 2015,46(6):730-733. doi: 10.11665/j.issn.1000-5048.20150616. doi: 10.11665/j.issn.1000-5048.20150616
[25]	赵祥月, 范宇超, 谢青昕, 等. 狂犬病疫苗脂质体冻干粉的免疫原性评价. 中国生物制品学杂志, 2020,33(3):250-253. doi: 10.13200/j.cnki.cjb.003001. doi: 10.13200/j.cnki.cjb.003001
[26]	Aneesh T, Pall TI, Signe TS, et al. Immunological and physical evaluation of the multistage tuberculosis subunit vaccine candidate H56/CAF01 formulated as a spray-dried powder. Vaccine, 2018,36(23):331-3339. doi: 10.1016/j.vaccine.2018.04.055. doi: 10.1016/j.vaccine.2018.04.055 URL
[27]	Cosgrove CA, Castello-Branco LR, Hussell T, et al. Boosting of cellular immunity against Mycobacterium tuberculosis and modulation of skin cytokine responses in healthy human volunteers by Mycobacterium bovis BCG substrain Moreau Rio de Janeiro oral vaccine. Infect Immun, 2006,74(4):2449-2452. doi: 10.1128/IAI.74.4.2449-2452.2006. doi: 10.1128/IAI.74.4.2449-2452.2006 URL
[28]	Hoft DF, Xia M, Zhang GL, et al. PO and ID BCG vaccination in humans induce distinct mucosal and systemic immune responses and CD4(+) T cell transcriptomal molecular signatures. Mucosal Immunol, 2018,11(2):486-495. doi: 10.1038/mi.2017.67. doi: 10.1038/mi.2017.67 pmid: 28853442
[29]	Magalhaes I, Sizemore DR, Ahmed RK, et al. rBCG induces strong antigen-specific T cell responses in rhesus macaques in a prime-boost setting with an adenovirus 35 tuberculosis vaccine vector. PLoS One, 2008,3(11):e3790. doi: 10.1371/journal.pone.0003790. doi: 10.1371/journal.pone.0003790 URL
[30]	Cai H, Yu DH, Hu XD, et al. A combined DNA vaccine-prime, BCG-boost strategy results in better protection against Mycobacterium bovis challenge. DNA Cell Biol, 2006,25(8):438-447. doi: 10.1089/dna.2006.25.438. doi: 10.1089/dna.2006.25.438 pmid: 16907641
[31]	Wang QM, Sun SH, Hu ZL, et al. Improved immunogenicity of a tuberculosis DNA vaccine encoding ESAT6 by DNA priming and protein boosting. Vaccine, 2004,22(27/28):3622-3627. doi: 10.1016/j.vaccine.2004.03.029. doi: 10.1016/j.vaccine.2004.03.029 URL
[32]	武亚琦. 成人结核病预防策略的探索性研究. 武汉: 华中科技大学, 2019. doi: 10.27157/d.cnki.ghzku.2019.005095. doi: 10.27157/d.cnki.ghzku.2019.005095
[33]	Andersen P, Smedegaard B. CD4(+) T-cell subsets that mediate immunological memory to Mycobacterium tuberculosis infection in mice. Infect Immun, 2000,68(2):621-629. doi: 10.1128/iai.68.2.621-629.2000. doi: 10.1128/iai.68.2.621-629.2000 pmid: 10639425
[34]	Bai C, He J, Niu H, et al. Prolonged intervals during Mycobacterium tuberculosis subunit vaccine boosting contributes to eliciting immunity mediated by central memory-like T cells. Tuberculosis (Edinb), 2018,110:104-111. doi: 10.1016/j.tube.2018.04.006. doi: 10.1016/j.tube.2018.04.006 URL
[35]	Kaveh DA, Garcia-Pelayo MC, Hogarth PJ. Persistent BCG bacilli perpetuate CD4 T effector memory and optimal protection against tuberculosis. Vaccine, 2014,32(51):6911-6918. doi: 10.1016/j.vaccine.2014.10.041. doi: 10.1016/j.vaccine.2014.10.041 URL

类别	抗原	佐剂/载体	佐剂/载体说明	临床阶段
添加佐剂的亚单位疫苗
M72	Rv1196+Rv0125	AS01	脂质体,TLR4受体激动剂	Ⅱb
H56	ESAT-6+Ag85B+Rv2660c	IC31	抗菌肽KLK+寡脱氧核苷酸ODN1a,TLR9受体激动剂	Ⅱb
ID93	Rv2608+Rv3619+Rv3620+Rv1813	GLA-SE	溶于水包油角鲨烯乳剂中的吡喃葡萄糖脂,TLR4受体激动剂	Ⅱa
GamTBvac	Ag85A+ESAT6-CFP10	CpG ODN	寡脱氧核苷酸,TLR9受体激动剂	Ⅱa
AEC/BC02	Ag85B+ESAT6+CFP10	CpG	基于CpG和铝盐的新型佐剂BC02	Ⅰ
重组病毒载体疫苗
TB/Flu-04L	Ag85A+ESAT6	Flu-04L	减毒复制缺陷流感病毒(H1N1)	Ⅱa
AERAS-402	Ag85A+Ag85B+TB10.4	rAd35	重组复制缺陷人腺病毒载体-35	Ⅱa
Ad5Ag85A	Ag85A	Ad5	重组复制缺陷人腺病毒载体-5	Ⅰ
ChAdOx185A+MVA85A boost	Ag85A	ChAdOx1、MVA	黑猩猩腺病毒、改良安卡拉牛痘病毒	Ⅰ