Frontiers in Biology

, Volume 13, Issue 4, pp 293–296 | Cite as

HspX protein as a candidate vaccine against Mycobacterium tuberculosis: an overview

  • Arshid Yousefi-Avarvand
  • Mohsen Tafaghodi
  • Saman SoleimanpourEmail author
  • Farzad Khademi



Tuberculosis (TB) is a contagious infectious disease caused by Mycobacterium tuberculosis (Mtb). This disease with two million deaths per year has the highest mortality rate among bacterial infections. The only available vaccine against TB is BCG vaccine. BCG is an effective vaccine against TB in childhood, however, due to some limitations, has not proper efficiency in adults. Also, BCG cannot produce an adequately protective response against reactivation of latent infections.


In the present study we will review the most recent findings about contribution of HspX protein in the vaccines against tuberculosis.


Therefore, many attempts have been made to improve BCG or to find its replacement. Most of the subunit vaccines for TB in various phases of clinical trials were constructed as prophylactic vaccines using Mtb proteins expressed in the replicating stage. These vaccines might prevent active TB but not reactivation of latent tuberculosis infection (LTBI). A literature search was performed on various online databases (PubMed, Scopus, and Google Scholar) regarding the roles of HspX protein in tuberculosis vaccines.


Ideal subunit post-exposure vaccines should target all forms of TB infection, including active symptomatic and dormant (latent) asymptomatic forms. Among these subunit vaccines, HspX is the most important latent phase antigen of M. tuberculosis with a strong immunological response. There are many studies that have evaluated the immunogenicity of this protein to improve TB vaccine.


According to the studies, HspX protein is a good candidate for development of subunit vaccines against TB infection.


HspX protein Mycobacterium tuberculosis vaccine 


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The authors are grateful to our colleagues in Mashhad University of Medical Sciences for their sincerely cooperation.


  1. Aagaard C, Dietrich J, Doherty M, Andersen P (2009). TB vaccines: current status and future perspectives. Immunol Cell Biol, 87(4): 279–286CrossRefPubMedGoogle Scholar
  2. Andersen P, Kaufmann S H (2014). Novel vaccination strategies against tuberculosis. Cold Spring HarbPerspect Med, 4(6): a018523CrossRefGoogle Scholar
  3. Britton W J, Palendira U (2003). Improving vaccines against tuberculosis. Immunol Cell Biol, 81(1): 34–45CrossRefPubMedGoogle Scholar
  4. Chen L, Xu M, Wang Z Y, Chen B W, Du W X, Su C, Shen X B, Zhao A H, Dong N, Wang Y J, Wang G Z (2010). The development and preliminary evaluation of a new Mycobacterium tuberculosis vaccine comprising Ag85b, HspX and CFP-10:ESAT-6 fusion protein with CpG DNA and aluminum hydroxide adjuvants. FEMS Immunol Med Microbiol, 59(1): 42–52CrossRefPubMedGoogle Scholar
  5. da Costa A C, Costa-Júnior A O, de Oliveira F M, Nogueira S V, Rosa J D, Resende D P, Kipnis A, Junqueira-Kipnis A P (2014). A new recombinant BCG vaccine induces specific Th17 and Th1 effector cells with higher protective efficacy against tuberculosis. PLoS One, 9(11): e112848CrossRefPubMedPubMedCentralGoogle Scholar
  6. de Sousa E M, da Costa A C, Trentini M M, de AraújoFilho J A, Kipnis A, Junqueira-Kipnis A P (2012). Immunogenicity of a fusion protein containing immunodominant epitopes of Ag85C, MPT51, and HspX from Mycobacterium tuberculosis in mice and active TBinfection. PLoS One, 7(10): e47781CrossRefPubMedPubMedCentralGoogle Scholar
  7. Geluk A, Lin M Y, van Meijgaarden K E, Leyten E M, Franken K L, Ottenhoff T H, Klein M R (2007). T-cell recognition of the HspX protein of Mycobacterium tuberculosis correlates with latent M. tuberculosis infection but not with M. bovis BCG vaccination. Infect Immun, 75(6): 2914–2921CrossRefPubMedPubMedCentralGoogle Scholar
  8. Jeon B Y, Kim S C, Eum S Y, Cho S N (2011). The immunity and protective effects of antigen 85A and heat-shock protein X against progressive tuberculosis. Microbes Infect, 13(3): 284–290CrossRefPubMedGoogle Scholar
  9. Jung I D, Shin S J, Lee MG, Kang T H, Han H D, Lee S J, Kim WS, Kim H M, Park WS, Kim H W, Yun C H, Lee E K, Wu T C, Park Y M (2014). Enhancement of tumor-specific T cell-mediated immunity in dendritic cell-based vaccines by Mycobacterium tuberculosis heat shock protein X. J Immunol, 193(3): 1233–1245CrossRefPubMedPubMedCentralGoogle Scholar
  10. Junqueira-Kipnis A P, Marques Neto L M, Kipnis A (2014). Role of fused Mycobacterium tuberculosis immunogens and adjuvants in modern Tuberculosis vaccines. Front Immunol, 5: 188CrossRefPubMedPubMedCentralGoogle Scholar
  11. Li Q, Yu H, Zhang Y, Wang B, Jiang W, Da Z, Xian Q, Wang Y, Liu X, Zhu B (2011). Immunogenicity and protective efficacy of a fusion protein vaccine consisting of antigen Ag85B and HspX against Mycobacterium tuberculosis infection in mice. S cand J Immunol, 73(6): 568–576CrossRefGoogle Scholar
  12. Liang J, Teng X, Yuan X, Zhang Y, Shi C, Yue T, Zhou L, Li J, Fan X (2015). Enhanced and durable protective immune responses induced by a cocktail of recombinant BCG strains expressing antigens of multistage of Mycobacterium tuberculosis. MolImmunol, 66(2): 392–401Google Scholar
  13. Lin M Y, Geluk A, Smith S G, Stewart A L, Friggen A H, Franken K L, Verduyn MJ, van Meijgaarden K E, Voskuil MI, Dockrell H M, Huygen K, Ottenhoff T H, Klein M R (2007). Lack of immune responses to Mycobacterium tuberculosis DosR regulon proteins following Mycobacterium bovis BCG vaccination. I nfect Immun, 75(7): 3523–3530CrossRefGoogle Scholar
  14. Marongiu L, Donini M, Toffali L, Zenaro E, Dusi S (2013). ESAT-6 and HspX improve the effectiveness of BCG to induce human dendritic cells-dependent Th1 and NKcells activation. PLoS One, 8(10): e75684CrossRefPubMedPubMedCentralGoogle Scholar
  15. Mir F A, Kaufmann S H, Eddine A N (2009). A multicistronic DNA vaccine induces significant protection against tuberculosis in mice and offers flexibility in the expressed antigen repertoire. Clin Vaccine Immunol, 16(10): 1467–1475CrossRefPubMedPubMedCentralGoogle Scholar
  16. Mosavat A, Soleimanpour S, Farsiani H, Sadeghian H, Ghazvini K, Sankian M, Jamehdar S A, Rezaee S A (2016). Fused Mycobacterium tuberculosis multi-stage immunogens with an Fcdelivery system as a promising approach for the development of a tuberculosis vaccine. Infect Genet Evol, 39: 163–172CrossRefPubMedGoogle Scholar
  17. Niu H, Hu L, Li Q, Da Z, Wang B, Tang K, Xin Q, Yu H, Zhang Y, Wang Y, Ma X, Zhu B (2011). Construction and evaluation of a multistage Mycobacterium tuberculosis subunit vaccine candidate Mtb10.4-HspX. Vaccine, 29(51): 9451–9458CrossRefPubMedGoogle Scholar
  18. Niu H, Peng J, Bai C, Liu X, Hu L, Luo Y, Wang B, Zhang Y, Chen J, Yu H, Xian Q, Zhu B (2015). Multi-Stage Tuberculosis Subunit Vaccine Candidate LT69 Provides High Protection against Mycobacterium tuberculosis Infection in Mice. PLoS One, 10(6): e0130641CrossRefPubMedPubMedCentralGoogle Scholar
  19. O’Garra A, Redford P S, McNab F W, Bloom C I, Wilkinson R J, Berry M P (2013). The immune response in tuberculosis. Annu Rev Immunol, 31(1): 475–527CrossRefPubMedGoogle Scholar
  20. Shi C, Chen L, Chen Z, Zhang Y, Zhou Z, Lu J, Fu R, Wang C, Fang Z, Fan X (2010). Enhanced protection against tuberculosis by vaccination with recombinant BCG over-expressing HspX protein. Vaccine, 28(32): 5237–5244CrossRefPubMedGoogle Scholar
  21. Silva B D, Tannus-Silva D G, Rabahi MF, Kipnis A, Junqueira-Kipnis A P (2014). The use of Mycobacterium tuberculosisHspX and GlcB proteins to identify latent tuberculosis in rheumatoid arthritis patients. Mem Inst Oswaldo Cruz, 109(1): 29–37CrossRefPubMedGoogle Scholar
  22. Soleimanpour S, Farsiani H, Mosavat A, Ghazvini K, Eydgahi M R, Sankian M, Sadeghian H, Meshkat Z, Rezaee S A (2015). APC targeting enhances immunogenicity of a novel multistage Fc-fusion tuberculosis vaccine in mice. ApplMicrobiol Biotechnol, 99(24): 10467–10480Google Scholar
  23. Taylor J L, Wieczorek A, Keyser A R, Grover A, Flinkstrom R, Karls R K, Bielefeldt-Ohmann H, Dobos K M, Izzo A A (2012). HspXmediated protection against tuberculosis depends on its chaperoning of a mycobacterial molecule. Immunol Cell Biol, 90(10): 945–954CrossRefPubMedPubMedCentralGoogle Scholar
  24. Trentini M M, de Oliveira F M, Gaeti M P, Batista A C, Lima E M, Kipnis A, Junqueira-Kipnis A P (2014). Microstructured liposome subunit vaccines reduce lung inflammation and bacterial load after Mycobacterium tuberculosis infection. Vaccine, 32(34): 4324–4332CrossRefPubMedGoogle Scholar
  25. Wang X, Zhang J, Liang J, Zhang Y, Teng X, Yuan X, Fan X (2015). Protection against Mycobacterium tuberculosis infection offered by a new multistage subunit vaccine correlates with increased number of IFN-γ + IL-2 + CD4 + and IFN-γ + CD8 + T cells. PLoS One, 10(3): e0122560CrossRefPubMedPubMedCentralGoogle Scholar
  26. Xin Q, Niu H, Li Z, Zhang G, Hu L, Wang B, Li J, Yu H, Liu W, Wang Y, Da Z, Li R, Xian Q, Wang Y, Zhang Y, Jing T, Ma X, Zhu B (2013). Subunit vaccine consisting of multi-stage antigens has high protective efficacy against Mycobacterium tuberculosis infection in mice. PLoS One, 8(8): e72745CrossRefPubMedPubMedCentralGoogle Scholar
  27. Yuan W, Dong N, Zhang L, Liu J, Lin S, Xiang Z, Qiao H, Tong W, Qin C (2012). Immunogenicity and protective efficacy of a tuberculosis DNA vaccine expressing a fusion protein of Ag85BEsat6- HspX in mice. Vaccine, 30(14): 2490–2497CrossRefPubMedGoogle Scholar
  28. Yuan X, Teng X, Jing Y, Ma J, Tian M, Yu Q, Zhou L, Wang R, Wang W, Li L, Fan X (2015). A live attenuated BCG vaccine overexpressing multistage antigens Ag85B and HspX provides superior protection against Mycobacterium tuberculosis infection. Appl Microbiol Biotechnol, 99(24): 10587–10595CrossRefPubMedGoogle Scholar

Copyright information

© Higher Education Press and Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Arshid Yousefi-Avarvand
    • 1
    • 2
  • Mohsen Tafaghodi
    • 3
  • Saman Soleimanpour
    • 1
    • 2
    • 4
    Email author
  • Farzad Khademi
    • 5
  1. 1.Antimicrobial Resistance Research Center, School of MedicineMashhad University of Medical SciencesMashhadIran
  2. 2.Department of Microbiology and Virology, School of MedicineMashhad University of Medical SciencesMashhadIran
  3. 3.Nanotechnology Research Center, School of PharmacyMashhad University of Medical SciencesMashhadIran
  4. 4.Reference Tuberculosis Laboratory of Northeast-IranMashhad University of Medical SciencesMashhadIran
  5. 5.Department of Microbiology, School of MedicineArdabil University of Medical SciencesArdabilIran

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