综述

基于重组病毒载体的结核病疫苗研究进展*

  • 王江鸿 ,
  • 王晓春 ,
  • 夏露 ,
  • 皮欣欣 ,
  • 武家高
展开
  • 安徽理工大学,安徽淮南 232001
王晓春

收稿日期: 2025-02-23

  网络出版日期: 2026-04-02

基金资助

*安徽理工大学医学专项培育重点项目(YZ2023H1B003);安徽理工大学医学专项培育一般项目(YZ2023H2C006)

Research progress on tuberculosis vaccines based on recombinant viral vectors

  • WANG Jianghong ,
  • WANG Xiaochun ,
  • XIA Lu ,
  • PI Xinxin ,
  • WU Jiagao
Expand
  • Anhui University of Science and Technology, Huainan 232001, China

Received date: 2025-02-23

  Online published: 2026-04-02

摘要

结核病(tuberculosis, TB)仍然是世界各地严重的公共卫生威胁,然而,唯一获得许可的卡介苗(bacillus calmette-guérin, BCG)功效有限。近几十年来,病毒载体疫苗发展迅速。重组活病毒载体疫苗能够模拟病原体入侵机体并诱导免疫应答的过程,具备形成长效免疫记忆和提供较强免疫保护性的能力系统。本文系统回顾了当前结核病病毒载体疫苗的最新研究进展,对正在进行临床试验的结核病病毒载体疫苗进行了系统的文献综述,对处于开发早期有发展潜力的候选疫苗进行评估和总结。本文可能为开发更有效的结核病重组病毒载体疫苗提供理论及实践支持。

本文引用格式

王江鸿 , 王晓春 , 夏露 , 皮欣欣 , 武家高 . 基于重组病毒载体的结核病疫苗研究进展*[J]. 包头医学院学报, 2026 , 42(1) : 85 -90 . DOI: 10.16833/j.cnki.jbmc.2026.01.015

Abstract

Tuberculosis is still a serious public health threat around the world. However, bacillus calmette-guérin (BCG), the only licensed vaccine, has limited efficacy. In recent decades, viral vector vaccines have developed rapidly. Recombinant live virus vector vaccine can simulate the process of pathogen invasion and induce immune response, and has the ability to form long-term immune memory and strong immune protection. This paper reviews the latest research progress of tuberculosis virus vector vaccines, systematically reviews the tuberculosis virus vector vaccines undergoing clinical trials, and evaluates and summarizes the candidate vaccines with development potential in the early stage of development. This article may provide theoretical and practical support for the development of a more effective tuberculosis recombinant virus vector vaccine.

参考文献

[1] Collins LH, Kaufmann SH. Prospects for better tuberculosis vaccines[J]. The Lancet Infectious Diseases, 2001, 1(1):21-28.
[2] Zhang B, Dheda M, Orme MT, et al. Tuberculosis vaccines: opportunities and challenges[J]. Respirology, 2018, 23(4):359-368.
[3] Gopalaswamy R, Subbian S. An update on tuberculosis vaccines[J]. Methods in Molecular Biology, 2022, 2410: 387-409.
[4] Boom WH, Schaible UE, Achkar JM, et al. The knowns and unknowns of latent mycobacterium tuberculosis infection[J]. The Journal of Clinical Investigation, 2021, 131(3): 33-39.
[5] Claudio B, Gagliardi MG. Mycobacterium tuberculosis infection of host cells in space and time[J]. FEMS Microbiology Reviews, 2019, 43(4): 341-361.
[6] Zhuang L, Ye Z, Li L, et al. Next-generation TB vaccines: progress, challenges, and prospects[J]. Vaccines, 2023, 11(8): 55-63.
[7] Bernard M. Poxvirus DNA replication[J]. Cold Spring Harbor Perspectives in Biology, 2013, 5(9): a010199.
[8] Emanuele S, Morena AD, Nicola Z, et al. New viral vectors for infectious diseases and cancer[J]. Seminars in Immunology, 2020, 50(8): 214-222.
[9] Khanna M, Rady H, Dai G, et al. Intranasal boosting with MVA encoding secreted mycobacterial proteins Ag85A and ESAT-6 generates strong pulmonary immune responses and protection against M.tuberculosis in mice given BCG as neonates[J]. Vaccine, 2021, 39(12): 1780-1787.
[10] Scriba JT, Tameris M, Mansoor N, et al. Correction: modified vaccinia ankara-expressing Ag85A, a novel tuberculosis vaccine, is safe in adolescents and children, and induces polyfunctional CD4+T cells[J]. European Journal of Immunology, 2011, 41(5): 1501-1501.
[11] Cai L, Wang Y, Liu J, et al. Recombinant Ad5 vector expressing Ag85B-ESAT-6 fusion protein enhances BCG-induced protective immunity against Mycobacterium tuberculosis in mice[J]. Vaccine, 2020, 38(45): 7165-7173.
[12] Li Y, Broad JT. Broad-spectrum infection of adenovirus in diverse cell lines and animal models[J]. Cellular and Molecular Biology, 2024, 60(5): 45-56.
[13] Wang Z. Comprehensive analysis of human adenovirus serotypes and their applications[J]. Virology Journal, 2022, 19(1): 102-115.
[14] Zhang H, Zhao X, Li M, et al. Ad35-vectored vaccine encoding multiple mycobacterium tuberculosis antigens induces robust T cell responses and protection in a murine model[J]. Vaccine, 2022, 40(23): 3218-3226.
[15] Chen H. Efficient gene delivery by Ad35 in specific cell types[J]. Gene Therapy and Molecular Biology, 2023, 27(3): 89-101.
[16] Hu Z, Wong KW, Zhao HM, et al. Sendai virus mucosal vaccination establishes lung-resident memory CD8 T cell immunity and boosts BCG-Primed protection against TB in mice[J]. Molecular Therapy, 2017, 25(5): 1248-1257.
[17] Fan XY, Hu ZD, Zhao HM, et al. A novel recombinant Sendai virus vector vaccine encoding multiple latent and acute antigens confers enhanced protection against Mycobacterium tuberculosis infection in murine models[J]. Vaccine, 2024, 42(20): 3536-3545.
[18] 范小勇, 胡志东, 赵慧敏, 等.整合表达潜伏期相关抗原的多相重组仙台病毒载体疫苗可诱导急性和结核分枝杆菌潜伏感染的免疫保护 [J]. 微生物与感染, 2024, 19 (1): 59-60.
[19] Li Y, Wang Z, Liu J, et al. Attenuated influenza virus vector expressing mycobacterium tuberculosis antigens activates dendritic cells and induces robust mucosal and systemic immune responses[J]. Vaccine, 2020, 38(42): 6653-6662.
[20] Ivanov AA, Shmakov AN, Snetkova VV, et al. Safety and immunogenicity of a live attenuated influenza virus vector vaccine expressing mycobacterium tuberculosis antigens: a first-in-human, open-label, phase 1 trial[J]. The Lancet Respiratory Medicine, 2023, 11(11): 1008-1019.
[21] Dragomira M. Human adenovirus type 26 basic biology and its usage as vaccine vector[J]. Reviews in Medical Virology, 2022, 32(6): e2338-e2338.
[22] Amara RR, Chackerian B, Gao GF, et al. Human immunodeficiency virus type 1-specific immune responses in primates upon sequential immunization with adenoviral vaccine carriers of human and simian serotypes[J]. Journal of Virology, 2004, 78(14):7392-7399.
[23] Patrick MN, Anne LG. MVA-85A, a novel candidate booster vaccine for the prevention of tuberculosis in children and adults[J]. Current Opinion in Molecular Therapeutics, 2010, 12(1): 124-134.
[24] Scriba TJ, Tameris MD, McShane H, et al. Dose-Finding study of the novel tuberculosis vaccine MVA85A in healthy BCG-vaccinated infants[J]. The Journal of Infectious Diseases, 2011, 203(12):1832-1843.
[25] Scriba JT, Michele T, Erica S, et al. A phase IIa trial of the new tuberculosis vaccine, MVA85A, in HIV- and/or mycobacterium tuberculosis-infected adults[J]. American Journal of Respiratory and Critical Care Medicine, 2012, 185(7): 769-778.
[26] Stylianou E, Griffiths K, Poyntz H, et al. Improvement of BCG protective efficacy with a novel chimpanzee adenovirus and a modified vaccinia ankara virus both expressing Ag85A[J]. Vaccine, 2015, 33(48): 6800-6808.
[27] Shen FC, Jacob D, Zhu T, et al. Optimization and scale-up of cell culture and purification processes for production of an adenovirus-vectored tuberculosis vaccine candidate[J]. Vaccine, 2016, 34(29): 3381-3387.
[28] Seder RA, McShane H, Zhang X, et al. Intranasal boosting with an adenovirus-vectored vaccine markedly enhances protection by parenteral mycobacterium bovis BCG immunization against pulmonary tuberculosis[J]. Infection and Immunity, 2006, 74(8):4634-4643.
[29] Fiona S, Zhou X. Human type 5 adenovirus-based tuberculosis vaccine: is the respiratory route of delivery the future[J]. Expert review of vaccines, 2014, 13(8): 927-930.
[30] Jeyanathan M, Fritz DK, Afkhami S, et al. Aerosol delivery, but not intramuscular injection, of Adenovirus-vectored tuberculosis vaccine induces Respiratory-mucosal immunity in humans[J]. JCI Insight, 2022, 7(3):341-350.
[31] Aderem A, Tameris MD, Mehra N, et al. The novel tuberculosis vaccine, AERAS-402, induces robust and polyfunctional CD4+ and CD8+ T cells in adults[J]. American journal of respiratory and critical care medicine, 2010, 181(12):1407-1417.
[32] Kagina MB, Tameris DM, Geldenhuys H, et al. The novel tuberculosis vaccine, AERAS-402, is safe in healthy infants previously vaccinated with BCG, and induces dose-dependent CD4 and CD8 T cell responses[J]. Vaccine, 2014, 32(45): 5908-5917.
[33] Zhanna B, Kira S, Berik K, et al. A new intranasal influenza vector-based vaccine TB/FLU-04L against tuberculosis: preclinical safety studies[J]. Drug Research, 2022, 72(5): 155-164.
[34] Kira S, Konstantin S, Andrey A, et al. Preclinical safety evaluation: acute and repeated-dose toxicity of a new intranasal recombinant vector vaccine TB/FLU-04L against tuberculosis[J]. Drug Research, 2022, 72(4): 215-219.
[35] Nelson MK, Qinfeng H, Sophia V, et al. Recombinant Pichinde viral vector expressing tuberculosis antigens elicits strong T cell responses and protection in mice[J]. Frontiers in Immunology, 2023, 14: 1127515.
[36] Zhidong H, Ling G, Chun-Ling L, et al. The profile of T cell responses in bacille calmette-guérin-primed mice boosted by a novel sendai virus vectored Anti-Tuberculosis vaccine[J]. Frontiers in immunology, 2018, 9: 91796.
[37] Doe JD MD, Smith JA, Evans JN, et al. A novel chimpanzee adenovirus vector with low human seroprevalence: improved systems for vector derivation and comparative immunogenicity[J]. Plos one, 2012, 7(7): e40385.
[38] Nawamin P, Naomi B, Janet P, et al. Using an effective TB vaccination regimen to identify immune responses associated with protection in the murine model[J]. Vaccine, 2021, 39(9): 1452-1462.
[39] Smith A, Johnson B. Species-specific differences in lung-resident memory T cell longevity between mice and humans[J]. Journal of immunology, 2024, 212(3): 567-575.
文章导航

/