The double-sided effects of Mycobacterium bovis bacillus Calmette-Guérin vaccine on helminthic infections – current data and future prospects
Keywords:
Mycobacterium bovis bacillus Calmette-Guérin, helminthic infections, alveolar echinococcosis, taeniosis, schistosomosis, trichinellosisAbstract
Bacillus Calmette–Guérin (BCG), a live attenuated strain derived from an isolate of Mycobacterium bovis, is one of the childhood vaccinations widely used against tuberculosis (TB). In addition to its effects on mycobacterial diseases, the information has shown the protection effect of BCG in helminthic diseases. In the current review, the role of BCG vaccine in non-specific protection helminthic infection is reviewed. In human alveolar echinococcosis (AE), treatment with BCG enhances host’s innate immune response against the parasite via the number and activation of monocytes. In cysticercosis, despite the enhancement of Th1-biased immune responses by coadministration of rcC1 plus BCG-DNA, the level of induced protection did not increase compared to immunization with rcC1 antigen alone. Also, pretreatment of mice with live BCG vaccine induced a high level of protection against subsequent parasite infection with Taenia taeniaeformis. The reduction of the parasite burden in mice infected with Mesocestoides corti that received two doses of BCG post-infection demonstrated the therapeutic effect of BCG. The protective potential of the schistosomula/BCG vaccine against Schistosoma japonicum in sheep study showed a reduction in the number of adult worms and mean faecal egg counts post-challenge. In trichinellosis, BCG can induce hyperplasia of the reticuloendothelial system and activation of macrophages in mice. Therefore, these data revealed that BCG vaccination can exert non-specific protective effects for the prevention of diseases other than tuberculosis. Medicinal doses of BCG may be considered a new approach to the treatment of helminth infections.
References
Pai T., Behr M., Dowdy D., Dheda K., Divangahi M., Boehme C., Ginsberg A., Swaminathan S., Spigelman M., Getahun H., Menzies D., Raviglione M. 2016. Tuberculosis. Nature Reviews Disease Primers 2: article number 16076. https://doi.org/10.1038/nrdp.2016.76
Curtis N., Sparrow A., Ghebreyesus T.A., Netea M.G. 2020. Considering BCG vaccination to reduce the impact of COVID-19. Lancet 395(10236): 1545–1546. https://doi.org/10.1016/s0140-6736(20)31025-4
Garly M.L., Martins C.L., Balé C., Baldé M.A., Hedegaard K.L., Gustafson P., Lisse I.M., Whittle H.C., Aaby P. 2003. BCG scar and positive tuberculin reaction associated with reduced child mortality in West Africa: a non-specific beneficial effect of BCG? Vaccine 21(21–22): 2782–2790. https://doi.org/10.1016/s0264-410x(03)00181-6
Roth A., Gustafson P., Nhaga A., Djana Q., Poulsen A., Garly M.L., Jensen H., Sodemann M., Rodriques A., Aaby P. 2005. BCG vaccination scar associated with better childhood survival in Guinea-Bissau. International Journal of Epidemiology 34(3): 540–547. https://doi.org/10.1093/ije/dyh392
Kristensen I., Fine P., Aaby P., Jensen H. 2000. Routine vaccinations and child survival: follow up study in Guinea-Bissau, West Africa. BMJ 321(7274): 1435–1438. https://doi.org/10.1136/bmj.321.7274.1435
Redelman-Sidi G., Glickman M.S., Bochner B.H. 2014. The mechanism of action of BCG therapy for bladder cancer – a current perspective. Nature Reviews Urology 11(3): 153–162. https://doi.org/10.1038/nrurol.2014.15
Shann F. 2010. The non-specific effects of vaccines. Archives of Disease in Childhood 95(9): 662–667. https://doi.org/10.1136/adc.2009.157537
Shann F. 2013. Nonspecific effects of vaccines and the reduction of mortality in children. Clinical Therapeutics 35(2):109–114. https://doi.org/10.1016/j.clinthera.2013.01.007
Corrêa-Oliveira R., Caldas I.R., Gazzinelli G. 2000. Natural versus drug-induced resistance in Schistosoma mansoni infection. Parasitology Today 16(9): 397–399. https://doi.org/10.1016/s0169-4758(00)01740-3
Finkelman F.D., Shea-Donohue T., Goldhill J., Sullivan C.A., Morris S.C., Madden K.B., Gause W.C., Urban Jr J.F. 1997. Cytokine regulation of host defense against parasitic gastrointestinal nematodes: lessons from studies with rodent models. Annual Review of Immunology 15(1): 505–533. https://doi.org/10.1146/annurev.immunol.15.1.505
Cooper P.J., Mancero T., Espinel M., Sandoval C., Lovato R., Guderian R.H., Nutman T.B. 2001. Early human infection with Onchocerca volvulus is associated with an enhanced parasite-specific cellular immune response. Journal of Infectious Diseases 183(11):1662–1668. https://doi.org/10.1086/320709
Cooper P.J., Nutman T.B. 2002. IgE and its role in parasitic helminth infection: implications for anti-IgE-based therapies. In: IgE and anti-IgE therapy in asthma and allergic disease. (Eds. R.B. Fick, P. Jardieu). CRC Press: 409–425.
Arts R.J., Moorlag S.J., Novakovic B., Li Y., Wang S.Y., Oosting M., Kumar V., Xavier R.J., Wijmenga C., Joosten L.A., Reusken C.B.E.M., Benn C.S., Aaby P., Koopmans M.P., Stunnenberg H.G., van Crevel R., Netea M.G. 2018. BCG vaccination protects against experimental viral infection in humans through the induction of cytokines associated with trained immunity. Cell Host and Microbe 23(1): 89–100. https://doi.org/10.1016/j.chom.2017.12.010
Kleinnijenhuis J., Quintin J., Preijers F., Benn C.S., Joosten L.A., Jacobs C., Van Loenhout J., Xavier R.J., Aaby P., Van Der Meer J.W., van Crevel R., Netea M.G. 2014. Long-lasting effects of BCG vaccination on both heterologous Th1/Th17 responses and innate trained immunity. Journal of Innate Immunity 6(2): 152–158. https://doi.org/10.1159/000355628
Mackaness G. 1964. The immunological basis of acquired cellular resistance. Journal of Experimental Medicine 120(1): 105–120. https://doi.org/10.1084/jem.120.1.105
Reuben J.M., Tanner C.E., Rau M.E. 1978. Immunoprophylaxis with BCG of experimental Echinococcus multilocularis infections. Infection and Immunity 21(1): 135–139. https://doi.org/10.1128/iai.21.1.135-139.1978
Reuben J., Tanner C., Portelance V. 1979. Protection of cotton rats against experimental Echinococcus multilocularis infections with BCG cell walls. Infection and Immunity 23(3): 582–586. https://doi.org/10.1128/iai.23.3.582-586.1979
Guo Y.J., Wu D., Wang K.Y., Sun S.H. 2007. Adjuvant effects of bacillus Calmette-Guerin DNA or CpG-oligonucleotide in the immune response to Taenia solium cysticercosis vaccine in porcine. Scandinavian Journal of Immunology 66(6): 619–627. https://doi.org/10.1111/j.1365-3083.2007.02013.x
Thompson R., Penhale W., White T., Pass D. 1982. BCG-induced inhibition and destruction of Taenia taeniaeformis in mice. Parasite Immunology 4(2): 93–99. https://doi.org/10.1111/j.1365-3024.1982.tb00422.x
White T., Thompson R., Penhale W. 1988. Studies on BCG immunotherapy in mice infected with Mesocestoides corti. International Journal for Parasitology 18(3): 389–393. https://doi.org/10.1016/0020-7519(88)90149-X
Xu S., Shi F., Shen W., Lin J., Wang Y., Ye P., Tian E., Qian C., Lin B., Shi Y. 1995. Vaccination of sheep against Schistosoma japonicum with either glutathione S-transferase, keyhole limpet haemocyanin or the freeze/thaw schistosomula/BCG vaccine. Veterinary Parasitology 58(4): 301–312. https://doi.org/10.1016/0304-4017(94)00735-u
Mahmoud A.A., Peters P.A., Civil R.H., Remington J.S. 1979. In vitro killing of schistosomula of Schistosoma mansoni by BCG and C. parvumactivated macrophages. Journal of Immunology 122(5): 1655–1657. https://doi.org/10.2196/41502
Grove D.I., Civil R.H. 1978. Trichinella spiralis: effects on the host-parasite relationship in mice of BCG (attenuated Mycobacterium bovis). Experimental Parasitology 44(2): 181–189. https://doi.org/10.1016/0014-4894(78)90096-6
Conraths F.J., Deplazes P. 2015. Echinococcus multilocularis: epidemiology, surveillance and stateof- the-art diagnostics from a veterinary public health perspective. Veterinary Parasitology 213(3–4): 149–161. https://doi.org/10.1016/j.vetpar.2015.07.027
Kotwa J.D., Isaksson M., Jardine C.M., Campbell G.D., Berke O., Pearl D.L., Mercer N.J., Osterman- Lind E., Peregrine A.S. 2019. Echinococcus multilocularis infection, southern Ontario, Canada. Emerging Infectious Diseases 25(2): 265–272. https://doi.org/10.3201/eid2502.180299
Heidari Z., Sharbatkhori M., Mobedi I., Mirhendi S.H., Nikmanesh B., Sharifdini M., Mohebali M., Zarei Z., Arzamani K., Kia E.B. 2019. Echinococcus multilocularis and Echinococcus granulosus in canines in North-Khorasan Province, northeastern Iran, identified using morphology and genetic characterization of mitochondrial DNA. Parasites and Vectors 12: 1–13. https://doi.org/ /10.1186/s13071-019-3859-z
Bakhtiar N.M., Spotin A., Mahami-Oskouei M., Ahmadpour E., Rostami A. 2020. Recent advances on innate immune pathways related to host–parasite cross-talk in cystic and alveolar echinococcosis. Parasites and Vectors 13(1): 1–8. https://doi.org/10.1186/s13071-020-04103-4
Ma X., Zhang X., Liu J., Liu Y., Zhao C., Cai H., Lei W., Ma J., Fan H., Zhou J. 2020. The correlations between Th1 and Th2 cytokines in human alveolar echinococcosis. BMC Infectious Diseases 20(1): 1–8. https://doi.org/10.1186/s12879-020-05135-y
Gottstein B., Wang J., Boubaker G., Marinova I., Spiliotis M., Müller N., Hemphill A. 2015. Susceptibility versus resistance in alveolar echinococcosis (larval infection with Echinococcus multilocularis). Veterinary Parasitology 213(3–4): 103–109. https://doi.org/10.1016/j.vetpar.2015.07.029
Bast Jr R.C., Zbar B., Borsos T., Rapp H.J. 1974. BCG and cancer. New England Journal of Medicine 290(26): 1458–1469. https://doi.org/10.1056/nejm197406272902605
Ribi E.E., Meyer T.J., Azuma I., Zbar R. 1973. Mycobacterial cell wall components in tumor suppression and regression. National Cancer Institute Monograph 39: 115–119.
Zbar B., Ribi E., Rapp H.J. 1973. An experimental model for immunotherapy. National Cancer Institute Monograph 39: 3–9.
Chung E.B., Zbar B., Rapp H.J. 1973. Tumor regression mediated by Mycobacterium bovis (strain BCG). Effects of isonicotinic acid hydrazide, cortisone acetate, and antithymocyte serum. Journal of the National Cancer Institute 51(1): 241–250. https://doi.org/10.1093/jnci/51.1.241
Blok B.A., Arts R.J., van Crevel R., Benn C.S., Netea M.G. 2015. Trained innate immunity as underlying mechanism for the long-term, nonspecific effects of vaccines. Journal of Leukocyte Biology 98(3): 347–356. https://doi.org/10.1189/jlb.5ri0315-096r
Uthayakumar D., Paris S., Chapat L., Freyburger L., Poulet H., De Luca K. 2018. Non-specific effects of vaccines illustrated through the BCG example: from observations to demonstrations. Frontiers in Immunology 9: article number 2869. https://doi.org/10.3389/fimmu.2018.02869
Arts R.J., Carvalho A., La Rocca C., Palma C., Rodrigues F., Silvestre R., Kleinnijenhuis J., Lachmandas E., Gonçalves L.G., Belinha A., Cunha C., Oosting M., Joosten L.A.B., Matarese G., van Crevel R., Netea M.G. 2016. Immunometabolic pathways in BCG-induced trained immunity. Cell Reports 17(10): 2562–2571. https://doi.org/10.1016/j.celrep.2016.11.011
Garc.a H.H., Gonzalez A.E., Evans C.A., Gilman R.H. 2003. Taenia solium cysticercosis. Lancet 362(9383): 547–556. https://doi.org/10.1016/S0140-6736(03)14117-7
Garcia H.H., Gonzalez A.E., Gilman R.H. 2003. Diagnosis, treatment and control of Taenia solium cysticercosis. Current Opinion in Infectious Diseases 16(5): 411–419. https://doi.org/10.1097/00001432-200310000-00007
Willingham III A.L., Engels D. 2006. Control of Taenia solium cysticercosis/taeniosis. Advances in Parasitology 61: 509–566. https://doi.org/10.1016/s0065-308x(05)61012-3
White Jr A., Robinson P., Kuhn R. 1997. Taenia solium cysticercosis: host-parasite interactions and the immune response. Chemical Immunology 66: 209–230.
Irizarry-Rovira A.R., Wolf A., Bolek M. 2007. Taenia taeniaeformis-induced metastatic hepatic sarcoma in a pet rat (Rattus norvegicus). Journal of Exotic Pet Medicine 16(1): 45–48. https://doi.org/10.1053/j.jepm.2006.11.008
Ekanayake S., Warnasuriya N., Samarakoon P., Abewickrama H., Kuruppuarachchi N., Dissanaike A. 1999. An unusual ‘infection’of a child in Sri Lanka, with Taenia taeniaeformis of the cat. Annals of Tropical Medicine and Parasitology 93(8): 869–873. https://doi.org/10.1080/00034989957871
Wilcox R.S., Bowman D.D., Barr S.C., Euclid J.M. 2009. Intestinal obstruction caused by Taenia taeniaeformis infection in a cat. Journal of the American Animal Hospital Association 45(2): 93–96. https://doi.org/10.5326/0450093
Al-Jashamy K., Islam M. 2007. Morphological study of Taenia taeniaeformis scolex under scanning electron microscopy using hexamethyldislazane. Annals of Microscopy 7: 80–83. http://www.microscopy. org.sg/journal /vol_7/page _80-83.pdf
Cabrera G., Espinoza I., Kemmerling U., Galanti N. 2010. Mesocestoides corti: morphological features and glycogen mobilization during in vitro differentiation from larva to adult worm. Parasitology 137(3): 373–384. https://doi.org/10.1017/s0031182009991454
Vendelova E., Hrčkov. G., Lutz M., Brehm K., Nono J. 2016. In vitro culture of Mesocestoides corti metacestodes and isolation of immunomodulatory excretory–secretory products. Parasite Immunology 38(7): 403–413. https://doi.org/10.1111/pim.12327
Koziol U., Dom.nguez M.F., Mar.n M., Kun A., Castillo E. 2010. Stem cell proliferation during in vitro development of the model cestode Mesocestoides corti from larva to adult worm. Frontiers in Zoology 7: 1–12. https://doi.org/10.1186/1742-9994-7-22
Hrčkova G., Velenbný S., Halton D., Maule A. 2002. Mesocestoides corti (syn. M. vogae): modulation of larval motility by neuropeptides, serotonin and acetylcholine. Parasitology 124(4): 409–421. https://doi.org/10.1017/S0031182001001329
Vendelova E., Camargo de Lima J., Lorenzatto K.R., Monteiro K.M., Mueller T., Veepaschit J., Grimm C., Brehm K., Hrčkov. G., Lutz M.B. 2016. Proteomic analysis of excretory-secretory products of Mesocestoides corti metacestodes reveals potential suppressors of dendritic cell functions. PLOS Neglected Tropical Diseases 10(10): e0005061. https://doi.org/10.1371/journal.pntd.0005061
Gryseels B., Polman K., Clerinx J., Kestens L. 2006. Human schistosomiasis. Lancet 368(9541): 1106–1118. https://doi.org/10.1016/s0140-6736(06)69440-3
Gray D.J., Ross A.G., Li Y.S., McManus D.P. 2011. Diagnosis and management of schistosomiasis. BMJ 342: article number 2651. https://doi.org/10.1136/bmj.d2651
Ross A.G., Vickers D., Olds G.R., Shah S.M., McManus D.P. 2007. Katayama syndrome. Lancet Infectious Diseases 7(3): 218–224. https://doi.org/10.1016/s1473-3099(07)70053-1
Ross A.G.P., Bartley P.B., Sleigh A.C., Olds G.R., Li Y., Williams G.M., McManus D.P. 2002. Schistosomiasis. New England Journal of Medicine 346(16): 1212–1220. https://doi.org/10.1056/nejmra012396
Cheever A.W., Hoffmann K.F., Wynn T.A. 2000. Immunopathology of schistosomiasis mansoni in mice and men. Immunology Today 21(9): 465–466. https://doi.org/10.1016/s0167-5699(00)01626-1
Pearce E.J., MacDonald A.S. 2002. The immunobiology of schistosomiasis. Nature Reviews Immunology 2(7): 499–511. https://doi.org/10.1038/nri843
de Jesus A.R., Silva A., Santana L.B., Magalhaes A., de Jesus A.A., de Almeida R.P., Rêgo M.A., Burattini M.N., Pearce E.J., Carvalho E.M. 2002. Clinical and immunologic evaluation of 31 patients with acute schistosomiasis mansoni. Journal of Infectious Diseases 185(1): 98–105. https://doi.org/10.1086/324668
Montenegro S.M., Miranda P., Mahanty S., Abath F.G., Teixeira K.M., Coutinho E.M., Brinkman J., Gonçalves I., Domingues L.A., Domingues A.L., Sher A., Wynn T.A. 1999. Cytokine production in acute versus chronic human schistosomiasis mansoni: the cross-regulatory role of interferon-γ and interleukin-10 in the responses of peripheral blood mononuclear cells and splenocytes to parasite antigens. Journal of Infectious Diseases 1179(6): 1502–1514. https://doi.org/10.1086/314748
Chiaramonte M.G., Cheever A.W., Malley J.D., Donaldson D.D., Wynn T.A. 2001. Studies of murine schistosomiasis reveal interleukin-13 blockade as a treatment for established and progressive liver fibrosis. Hepatology 34(2): 273–282. https://doi.org/10.1053/jhep.2001.26376
Ribeiro de Jesus A., Magalhaes A., Gonzalez Miranda D., Gonzalez Miranda R., Ara.jo M.I., Almeida de Jesus A., Silva A., Santana L.B., Pearce E., Carvalho E.M. 2004. Association of type 2 cytokines with hepatic fibrosis in human Schistosoma mansoni infection. Infection and Immunity 72(6): 3391–3397. https://doi.org/10.1128/IAI.72.6.3391-3397.2004
La Flamme A.C., Patton E.A., Bauman B., Pearce E.J. 2001. IL-4 plays a crucial role in regulating oxidative damage in the liver during schistosomiasis. Journal of Immunology 166(3): 1903–1911. https://doi.org/10.4049/jimmunol.166.3.1903
Patton E.A., La Flamme A.C., Pedras-Vasoncelos J.A., Pearce E.J. 2002. Central role for interleukin-4 in regulating nitric oxide-mediated inhibition of T-cell proliferation and gamma interferon production in schistosomiasis. Infection and Immunity 70(1): 177–184. https://doi.org/10.1128/IAI.70.1.177-184.2002
Mitreva M., Jasmer D.P., Zarlenga D.S., Wang Z., Abubucker S., Martin J., Taylor C.M., Yin Y., Fulton L., Minx P. et al. 2011. The draft genome of the parasitic nematode Trichinella spiralis. Nature Genetics 43(3): 228–235. https://doi.org/10.1038/ng.769
Sun G.G., Song Y.Y., Jiang P., Ren H.N., Yan S.W., Han Y., Liu R.D., Zhang X., Wang Z.Q., Cui J. 2018. Characterization of a Trichinella spiralis putative serine protease. Study of its potential as serodiagnostic tool. PLOS Neglected Tropical Diseases 12(5): e0006485. https://doi.org/10.1371/journal.pntd.0006485
Zhang N., Li W., Fu B. 2018. Vaccines against Trichinella spiralis: progress, challenges and future prospects. Transboundary and Emerging Diseases 65(6): 1447–1458. https://doi.org/10.1111/tbed.12917
Rawla P., Sharma S. 2023. Trichinella spiralis. StatPearls
[Internet]. StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK538511/
Mu.oz-Carrillo J.L., Contreras-Cordero J.F., Mu.oz-L.pez J.L., Maldonado-Tapia C., Mu.oz- Escobedo J.J., Moreno-Garc.a M.A. 2017. Resiniferatoxin modulates the Th1 immune response and protects the host during intestinal nematode infection. Parasite Immunology 39(9): e12448. https://doi.org/10.1111/pim.12448
Bruschi F., Chiumiento L. 2012. Immunomodulation in trichinellosis: does Trichinella really escape the host immune system? Endocrine, Metabolic and Immune Disorders-Drug Targets 12(1): 4–15. https://doi.org/10.2174/187153012799279081
Aranzamendi C., de Bruin A., Kuiper R., Boog C.J., Van Eden W., Rutten V., Pinelli E. 2013. Protection against allergic airway inflammation during the chronic and acute phases of Trichinella spiralis infection. Clinical and Experimental Allergy 43(1): 103–115. https://doi.org/10.1111/cea.12042
Wang N., Bai X., Tang B., Yang Y., Wang X., Zhu H., Luo X., Yan H., Jia H., Liu M. 2020. Primary characterization of the immune response in pigs infected with Trichinella spiralis. Veterinary Research 51(1): 1–14. https://doi.org/10.1186/s13567-020-0741-0
Despommier D., Campbell W., Blair L. 1977. The in vivo and in vitro analysis of immunity to Trichinella spiralis in mice and rats. Parasitology 74(1): 109–119. https://doi.org/10.1017/S0031182000047570
