Skip to main content

Advertisement

SpringerLink
Log in

Role of Mycobacterium vaccae in the protection induced by first generation Leishmania vaccine against murine model of leishmaniasis

  • Original Paper
  • Published:
Parasitology Research Aims and scope Submit manuscript

Abstract

Various Leishmania antigens showed to induce protection when used with IL-12 as an adjuvant in an animal model of leishmaniasis. Limitations in using IL-12 justify searching for an appropriate adjuvant to accelerate induction of a Th1-type immune response and protection. In this study, the role of Mycobacterium vaccae as an adjuvant mixed with either autoclaved Leishmania major (ALM) or freeze–thawed-killed L. major (KLM) in increasing protection in susceptible and resistant mice was studied. Nineteen groups of BALB/c and 19 groups of C57BL/6 mice, ten mice per group, were immunized three times in 45 days interval with different doses of either KLM or ALM alone or mixed with either BCG or different doses of M. vaccae. Immunized groups of mice and PBS-injected control group were challenged with 2 × 106 promastigotes of L. major at the base of the tail. The evolution of the lesion was monitored, and the size of the lesion was measured and recorded weekly. Anti-Leishmania total IgG Ab was titrated before and after challenge. The results showed that immunization of either susceptible or resistant mice with KLM or ALM mixed with low dose of M. vaccae increased protection defined by significantly smaller ulcer size in immunized mice compared with the PBS-injected control group.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

Abbreviations

ALM:

Autoclaved Leishmania major

KLM:

Killed Leishmania major

BCG:

Bacillus Calmette–Guérin

References

  • Alimohammadian M, Khamesipour A, Darabi H, Firooz A, Malekzadeh S (2002) The role of BCG in human immune responses induced by multiple injections of autoclaved L. major as a candidate vaccine against leishmaniasis. Vaccine 21:174–180

    Article  PubMed  CAS  Google Scholar 

  • Andersen P, Doherty TM (2005) The success and failure of BCG implications for a novel tuberculosis vaccine. Nat Rev Microbiol 3:656–662

    Article  PubMed  CAS  Google Scholar 

  • Armijos RX, Weigel MM, Aviles H, Maldonado R, Racines J (1998) Field trial of a vaccine against new world cutaneous leishmaniasis in an at-risk child population: safety, immunogenicity and efficacy during 12 months of follow up. J Infect Dis 177:1352–1357

    Article  PubMed  CAS  Google Scholar 

  • Armijos RX, Weigel MM, Calvopina M, Hidalgo A, Cevallos W, Correa J (2004) Safety, immunogenecity, and efficacy of an autoclaved Leishmania amazonensis vaccine plus BCG adjuvant against New World cutaneous leishmaniasis. Vaccine 22(9–10):1320–1356

    Article  PubMed  CAS  Google Scholar 

  • Assersohn L, Souberbielle BE, O’Brien ME, Archer CD, Mendes R, Bass R, Bromelow KV, Palmer RD, Bouilloux E, Kennard DA, Smith IE (2002) A randomized pilot study of SRL172 (Mycobacterium vaccae) in patients with small cell lung cancer (SCLC) treated with chemotherapy. Clin Oncol (R Coll Radiol) 14:23–27

    CAS  Google Scholar 

  • Bahar K, Dowlati Y, Shidani B, Alimohammadian M, Khamesipour A (1996) Comparative safety and immunogenicity trial of two killed L. major vaccines with or without BCG in human volunteers. Clin Dermatol 14:489–495

    Article  PubMed  CAS  Google Scholar 

  • Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein dye binding. Anal Biochem 72:248–254

    Article  PubMed  CAS  Google Scholar 

  • Cabrera M, Blackwell JM, Castes M, Trujillo D, Convit J (2000) Immunotherapy with live BCG plus heat killed Leishmania induces a T helper 1 like response in American cutaneous leishmaniasis patients. Parasite Immunol 22:73–79

    Article  PubMed  CAS  Google Scholar 

  • Camporota L, Corkhill A, Long H, Lordan J, Stanciu L, Tuckwell N, Cross A, Stanford JL, Rook GA, Holgate ST, Djukanovic R (2003) The effects of Mycobacterium vaccae on allergen-induced airway responses in atopic asthma. Eur Respir J 21:287–293

    Article  PubMed  CAS  Google Scholar 

  • Convit J, Castellanos PL, Urich M, Castes M, Rondon A (1989) Immunotherapy of localized, intermediate and diffuse forms of American cutaneous leishmaniasis. J Infect Dis 160:104–115

    PubMed  CAS  Google Scholar 

  • De Luca PM, Mayrink W, Alve CR, Coutinho SG, Oliveira MP, Bertho AL, Toledo VP, Costa CA, Genaro O, Mendonca SCF (1999) Evaluation of the stability and immunogenicity of autoclaved and non-autoclaved cutaneous preparations of a vaccine against American tegumentary leishmaniasis. Vaccine 17:1179–1185

    Article  PubMed  Google Scholar 

  • Dlugovitzky D, Fiorenza G, Farroni M, Bogue C, Stanford C, Stanford J (2006) Immunological consequences of three doses of heat-killed Mycobacterium vaccae in the immunotherapy of tuberculosis. Respir Med 100:1079–1087

    Article  PubMed  Google Scholar 

  • Farid R, Etemadi A, Mehvar M, Stanford JL, Dowlati Y (1994) Mycobacterium vaccae immunotherapy in the treatment of multi-drug resistant tuberculosis: a preliminary report. Iran J Med Sci 19:37–39

    Google Scholar 

  • Frommel D, Lagrange PH (1989) BCG: a modifier of immune response to parasites. Parasitol Today 5:188–190

    Article  PubMed  CAS  Google Scholar 

  • Grange JM, Stanford JL (1995) Tuberculosis and cancer: parallels in host responses and therapeutic approaches. Lancet 345:1350–1352

    Article  PubMed  CAS  Google Scholar 

  • Hadley EA, Smillie FI, Turner MA, Custovic A, Woodcock A, Arkwright PD (2005) Effect of Mycobacterium vaccae on cytokine responses in children with atopic dermatitis. Clin Exp Immunol 140:101–108

    Article  PubMed  CAS  Google Scholar 

  • Hernandez-Pando R, Pavon L, Arriaga K, Orozco H, Madrid-Marina V (1997) Pathogenesis of tuberculosis in mice exposed to low and high doses of an environmental mycobacterial saprophyte before infection. Infect Immun 65:3317–3327

    PubMed  CAS  Google Scholar 

  • Hrouda D, Souberbielle BE, Kayaga J, Corbishley CM, Kirby RS, Dalgleish AG (1998) Mycobacterium vaccae (SRL172): a potential immunological adjuvant evaluated in rat prostate cancer. Br J Urol 82:870–876

    PubMed  CAS  Google Scholar 

  • Kamil AA, Khalil EA, Musa AM, Modabber F, Mukhtar MM (2003) Alum-precipitated autoclaved L. major plus BCG a candidate vaccine for visceral leishmaniasis: safety, skin delayed type hypersensitivity response and dose finding in healthy volunteers. Trans R Soc Trop Med Hyg 97:365–368

    Article  PubMed  CAS  Google Scholar 

  • Kemp K, Hviid L, Kharazmi A, Kemp M (1997) Interferon-gamma production by human T cells and natural killer cells in vitro in response to antigen from the two intracellular pathogens M. tuberculosis and L. major. Scan J Immunol 46:495–499

    Article  CAS  Google Scholar 

  • Kenney RT, Sacks DL, Sypek JP, Vilela L, Gam AA, Evans-Davis K (1999) Protective immunity using recombinant human IL-12 and alum as adjuvants in a primate model of cutaneous leishmaniasis. J Immunol 163:4481–4488

    PubMed  CAS  Google Scholar 

  • Khalil EAG, El-Hassan AM, Zijlstra EE, Mukhtar MM, Ghalib HW (2000) Autoclaved L. major vaccine for prevention of visceral leishmaniasis: a randomized double-blind BCG-controlled trial in Sudan. Lancet 356:1565–1569

    Article  PubMed  CAS  Google Scholar 

  • Khamesipour A, Rafati S, Davoudi N, Mahboudi F, Modabber F (2006) Leishmaniasis vaccine candidates for development: global overview. Indian J Med Res 123:423–438

    PubMed  Google Scholar 

  • Lagranderie MRR, Balazuc AM (1996) Comparison of immune responses of mice immunized with five different M. bovis BCG vaccine strains. Infect Immun 64:1–9

    PubMed  CAS  Google Scholar 

  • Mahmoodi M, Khamesipour A, Dowlati Y, Rafati S, Momeni AZ (2003) Immune response measured in human volunteers vaccinated with autoclaved L. major vaccine mixed with low dose of BCG. Clin Exp Immunol 134:303–308

    Article  PubMed  CAS  Google Scholar 

  • Marzochi KB, Marzochi MA, Silva AF, Grativol N, Duarte R, Confort EM, Modabber F (1998) Phase 1 study of an inactivated vaccine against American tegumentary leishmaniasis in normal volunteers in Brazil. Mem Inst Oswaldo Cruz 93:205–212

    Article  PubMed  CAS  Google Scholar 

  • Marshall BG, Chambers MA, Wangoo A, Shaw RJ, Young DB (1997) Production of tumor necrosis factor and nitric oxide by macrophages infected with live and dead Mycobacteria and their suppression by an IL-10 secreting recombinant. Infect Immun 65:1931–1935

    PubMed  CAS  Google Scholar 

  • Mendes R, O’Brien ME, Mitra A, Norton A, Gregory RK, Padhani AR, Bromelow KV, Winkley AR, Ashley S, Smith IE, Souberbielle BE (2002) Clinical and immunological assessment of Mycobacterium vaccae (SRL172) with chemotherapy in patients with malignant mesothelioma. Br J Cancer 86:336–341

    Article  PubMed  CAS  Google Scholar 

  • Misra A, Dube A (2001) Successful vaccination against L. donovani infection in Indian langur using Alum precipitated autoclaved L. major with BCG. Vaccine 19:3485–3492

    Article  PubMed  CAS  Google Scholar 

  • Modabber F (2000) First generation Leishmaniasis vaccine clinical development: moving but what next? Curr Opin Anti-infect Invest Drug 2:35–39

    Google Scholar 

  • Mohebali M, Khamesipour A, Mobedi I, Zarei Z, Hashemi-Fesharaki R (2004) Double blind randomized efficacy field trial of alum precipitated autoclaved L. major vaccine mixed with BCG against canine visceral leishmaniasis in Meshkin-Shahr district, I.R.Iran. Vaccine 22:4097–4100

    Article  PubMed  CAS  Google Scholar 

  • Momeni AZ, Jalayer T, Emamjomeh T, Khamesipour A, Zicker F (1999) A randomized double blind controlled trial of a killed L. major vaccine plus BCG against zoonotic cutaneous leishmaniasis in Iran. Vaccine 17:466–472

    Article  PubMed  CAS  Google Scholar 

  • Murray HW, Berman JD, Davies CR, Saravia NG (2005) Advances in leishmaniasis. Lancet 366:1561–77

    Article  PubMed  CAS  Google Scholar 

  • Mwinga A, Nunn A, Ngwira B, Chintu C, Warndorff D, Fine P, Darbyshire J, Zumla A (2002) Mycobacterium vaccae (SRL172) immunotherapy as an adjunct to standard antituberculosis treatment in HIV-infected adults with pulmonary tuberculosis: a randomised placebo-controlled trial. Lancet 360:1050–1055

    Article  PubMed  Google Scholar 

  • Ozdemir C, Akkoc T, Bahceciler NN, Kucukercan D, Barlan IB, Basaran MM (2003) Impact of Mycobacterium vaccae immunization on lung histopathology in a murine model of chronic asthma. Clin Exp Allergy 33:266–270

    Article  PubMed  CAS  Google Scholar 

  • Sacks D, Noben-Trauth N (2002) The immunology of susceptibility and resistance to Leishmania major in mice. Nat Rev Immunol 2:845–58

    Article  PubMed  CAS  Google Scholar 

  • Scott P, Natovits P (1988) Immunoregulation of cutaneous leishmaniasis. T cell lines that transfer protective immunity or exacerbation belong to different T helper subsets and respond to distinct parasite antigens. J Exp Med 168:1675–84

    Article  PubMed  CAS  Google Scholar 

  • Sharifi I, Fekri AR, Aflatonian MR, Khamesipour A, Nadim A (1998) Randomised vaccine trial of single dose of killed L. major plus BCG against anthroponotic cutaneous leishmaniasis in Bam, Iran. Lancet 351:1540–1543

    Article  PubMed  CAS  Google Scholar 

  • Shoenfeld Y, Isenberg DA (1988) Mycobacteria and autoimmunity. Immunol Today 9:178–82

    Article  PubMed  CAS  Google Scholar 

  • Skinner MA, Yuan S, Prestidge R, Chuk D, Watson JD (1997) Immunization with heat-killed M. vaccae stimulates CD8 cytotoxic T cells specific for macrophages infected with M. tuberculosis. Infect Immun 65(11):4525–4530

    PubMed  CAS  Google Scholar 

  • Skinner MA, Prestidge R, Yuan S, Strabala TJ, Tan PL (2001) The ability of heat-killed Mycobacterium vaccae to stimulate a cytotoxic T-cell response to an unrelated protein is associated with a 65 kilodalton heat-shock protein. Immunology 102:225–233

    Article  PubMed  CAS  Google Scholar 

  • Torisu M, Miyahara T, Shinohara N, Ohasto K, Sonozaki H (1978) A new side effect of BCG immunotherapy—BCG induced arthritis in man. Cancer Immunol Immunother 5:77–83

    Article  Google Scholar 

  • Waddell RD, Chintu C, Lein AD, Zumla A, Karagas MR, Baboo KS, Habbema JD, Tosteson AN, Morin P, Tvaroha S, Arbeit RD, Mwinga A, von Reyn CF (2000) Safety and immunogenicity of a five-dose series of inactivated Mycobacterium vaccae vaccination for the prevention of HIV-associated tuberculosis. Clin Infect Dis 30(Suppl 3):S309–S315

    Article  PubMed  Google Scholar 

  • WHO SWG (2004) Report on leishmaniasis. TDR/SWG/04; Geneva, 2004

  • Zuany-Amorim C, Sawicka E, Manlius C, Le MA, Brunet LR, Kemeny DM, Bowen G, Rook G, Walker C (2002) Suppression of airway eosinophilia by killed Mycobacterium vaccae-induced allergen-specific regulatory T-cells. Nat Med 8:625–629

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was financially supported by the Center for Research and Training in Skin Diseases and Leprosy, Medical Sciences/University of Tehran, Tehran, Iran. The authors would also like to thank Dr. J. Stanford for the donation of M. vaccae. KLM and ALM were donated by Dr. R. Hashemi-Fesharki, Razi Vaccine and Serum Research Institute, Iran. The authors declare that the experiments comply with the official laws of the Islamic Republic of Iran.

Author information

Author notes

  1. Ali Khamesipour

    Present address: , P. O. Box 14155-6383, Tehran, 14166, Iran

Authors and Affiliations

  1. Medical Parasitology and Mycology Department, School of Public Health and Institute of Public Health Research, Medical Sciences/University of Tehran, Tehran, Iran

    Hosein Keshavarz Valian, Lavinia Khoshabe Abdollah Kenedy & Mahmoud Nateghi Rostami

  2. Center for Research and Training in Skin Diseases and Leprosy, Medical Sciences/University of Tehran, Tehran, Iran

    Akram Miramin Mohammadi & Ali Khamesipour

Authors
  1. Hosein Keshavarz Valian
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lavinia Khoshabe Abdollah Kenedy
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mahmoud Nateghi Rostami
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Akram Miramin Mohammadi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ali Khamesipour
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ali Khamesipour.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Keshavarz Valian, H., Khoshabe Abdollah Kenedy, L., Nateghi Rostami, M. et al. Role of Mycobacterium vaccae in the protection induced by first generation Leishmania vaccine against murine model of leishmaniasis. Parasitol Res 103, 21–28 (2008). https://doi.org/10.1007/s00436-008-0921-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00436-008-0921-8

Keywords

Search

Navigation