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Tuberculosis Vaccine: Past Experiences and Future Prospects

  • Gurpreet Kaur
  • Deepjyoti K. Das
  • Sanpreet Singh
  • Junaid Khan
  • Mohammad Sajid
  • Hilal Bashir
  • Mohammad Aqdas
  • Shikha Negi
  • Uthaman Gowthaman
  • Javed N. AgrewalaEmail author
Chapter

Abstract

Vaccines are the best prophylactic measure that have eradicated several diseases like polio, measles, and small pox. Currently, efficient vaccines are unavailable for many dreaded diseases, including tuberculosis (TB). TB is caused by an intracellular pathogen Mycobacterium tuberculosis (Mtb) and is responsible for about two million deaths and nine million new cases annually. The WHO has announced TB as a global emergency in the wake of emerging multidrug-resistant, extremely drug-resistant, and totally drug-resistant strains of Mtb. An alarming increase in the number of TB cases around the world and its co-occurrence with HIV has further complicated the problem. Additionally, BCG has failed in reducing the global TB burden, despite its widespread usage. Interestingly, BCG protects children from TB, indicating that it has sufficient antigenic repertoire to protect against Mtb. In contrast, failure to protect adults, suggests BCG inability to generate long-lasting immunological memory. Further, protection rendered by BCG against pulmonary TB in adults is highly inconsistent, varying from 0% to 85% (Andersen and Doherty, Nat Rev Microbiol 3:656–62, 2005). Furthermore, its efficacy is least in TB-endemic countries. Studies conducted in Malawi, India, and other endemic countries have concluded that BCG induces inadequate protection. The probable reasons suggested are the interference by nontuberculous mycobacteria (NTM) in antigen processing and presentation of antigen-presenting cells (APCs), latent TB infection (LTBI), and high prevalence of helminth infestation. There are currently 12 vaccine candidates in clinical trials, including recombinant BCG vaccines, attenuated Mtb strains, recombinant viral-vectored platforms, protein/adjuvant combinations, and mycobacterial extracts (WHO, Global tuberculosis report, 2017). However, the whole-cell vaccine candidates may encounter same problem in TB-endemic population, as mentioned above for BCG. Therefore, radically novel strategies of vaccination against Mtb are urgently needed. Peptide vaccines can be a possible alternative to overcome the failures of BCG because it comprises of epitopes that can directly bind to MHC molecules, circumventing the interference of NTM and latent Mtb in antigen processing. Furthermore, epitopes from multiple stages like LTBI, active, chronic, and drug-resistant Mtb can be selected. In essence, peptide-based prophylactic and therapeutic vaccines represent a promising future strategy for efficient management of TB.

Keywords

Mycobacterium tuberculosis Immune response Vaccines Peptide vaccines 

Abbreviations

APCs

Antigen-presenting cells

DCs

Dendritic cells

DIM

Phthiocerol dimycocerosates

Hly

Listeriolysin

LTBI

Latent TB infection

Mtb

Mycobacterium tuberculosis

NTM

Nontuberculous mycobacteria

PBMCs

Peripheral blood mononuclear cells

pfo

Perfringolysin

SNP

Single nucleotide polymorphisms

TB

Tuberculosis

Tregs

T regulatory cells

WHO

World Health Organization

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Copyright information

© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  • Gurpreet Kaur
    • 1
    • 2
  • Deepjyoti K. Das
    • 1
  • Sanpreet Singh
    • 1
  • Junaid Khan
    • 1
  • Mohammad Sajid
    • 1
  • Hilal Bashir
    • 1
  • Mohammad Aqdas
    • 1
  • Shikha Negi
    • 1
  • Uthaman Gowthaman
    • 3
  • Javed N. Agrewala
    • 1
    • 2
    Email author
  1. 1.Immunology LaboratoryInstitute of Microbial TechnologyChandigarhIndia
  2. 2.Centre for Biomedical EngineeringIndian Institute of Technology-RoparRupnagarIndia
  3. 3.Department of Laboratory Medicine, Immunobiology and OrthopedicsYale University School of MedicineNew HavenUSA

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